WO2017147407A1 - Compositions et procédés pour les préparer et les utiliser - Google Patents

Compositions et procédés pour les préparer et les utiliser Download PDF

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Publication number
WO2017147407A1
WO2017147407A1 PCT/US2017/019333 US2017019333W WO2017147407A1 WO 2017147407 A1 WO2017147407 A1 WO 2017147407A1 US 2017019333 W US2017019333 W US 2017019333W WO 2017147407 A1 WO2017147407 A1 WO 2017147407A1
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WIPO (PCT)
Prior art keywords
composition
nanoparticle
less
nanovesicles
silicon
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PCT/US2017/019333
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English (en)
Inventor
Brian Korgel
Dorothy SILBAUGH
Nora Ventosa
Lidia Priscila FERRER TASIES
Jaume Veciana
Original Assignee
Board Of Regents, The University Of Texas System
Consejo Superior De Investigaciones Cientificas
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Publication of WO2017147407A1 publication Critical patent/WO2017147407A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/5432—Liposomes or microcapsules
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54346—Nanoparticles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex

Definitions

  • Nanoparticles have been studied for a variety of applications, many of which can require the nanoparticles to be dispersible in water.
  • One approach to achieve dispersability in water for hydrophobic nanoparticles is to use colloidal vehicles, such as micelles, vesicles and polymer nanoparticles, for their stabilization in aqueous media.
  • Vesicular structures like liposomes which mimic cell membranes and are formed by bilayers of amphiphilic molecules, offer hydrophobic regions in the bilayer which can interact with hydrophobic particles.
  • the translation of liposomal formulations to real- world applications have been hindered by the tendency of these lipid self-assemblies to aggregate and by their low degree of structural homogeneity.
  • the compositions and methods disclosed herein address these and other needs.
  • compositions and methods relate to compositions and methods of making and using the compositions.
  • compositions comprising an aqueous solution comprising a composite nanocarrier, the composite nanocarrier comprising a nanoparticle at least partially encapsulated within a vesicle.
  • the vesicle can have an average size of from 25 to 500 nm as measured by dynamic light scattering (e.g., from 50 nm to 300 nm).
  • the vesicle can be substantially spherical in shape.
  • the vesicle can comprise a sterol and a surfactant.
  • the vesicle can, for example, be formed by self-assembly of the sterol and the surfactant.
  • a lipid is not a surfactant, such that the vesicles are not liposomes.
  • the sterol and the surfactant can be present in the vesicle in a molar ratio of from 10:1 to 1:5 (e.g., from 2:1 to 1:2). In some examples, the sterol and the surfactant can be present in the vesicle in a molar ratio of 1 : 1.
  • the surfactant comprises a quaternary ammonium surfactant, such as cetyl trimethylammonium bromide.
  • the vesicle comprises a sterol and a quaternary ammonium surfactant.
  • the vesicle consists of a sterol and a quaternary ammonium surfactant.
  • the sterol comprises cholesterol or a derivative thereof.
  • the sterol consists of cholesterol or a derivative thereof.
  • the nanoparticle that can be used in the compositions disclosed herein can comprise, for example, a semiconductor.
  • the nanoparticle can comprise a semiconductor such as Fe203, WO3, Ta3N 5 , TaON, T1O2, ZnO, CdS, CdSe, Si, or combinations thereof.
  • the nanoparticle can comprise Si.
  • the nanoparticle that can be used in the compositions disclosed herein can comprise, for example, a metal.
  • the nanoparticle can comprise a metal selected from the group consisting of Be, Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, In, Sn, Ba, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and combinations thereof.
  • the nanoparticle can comprise a magnetic nanoparticle.
  • the magnetic nanoparticle can comprise any suitable material, for example Fe, Co, Zn, Ni, Mn, Ag, Au, C, Cd, or a combination thereof.
  • the magnetic nanoparticle can comprise any suitable metal compound, such as an oxide of Fe, Co, Zn, Ni, Mn, or a combination thereof.
  • the magnetic nanoparticle comprise an iron oxide, for example Fe30 4 .
  • the nanoparticle can comprise a plasmonic nanoparticle.
  • the plasmonic nanoparticle can any suitable material, for example Au, Ag, Pd, and combinations thereof.
  • the nanoparticle can comprise a fluorescent nanoparticle.
  • the nanoparticle can be biocompatible.
  • the nanoparticle can be substantially spherical in shape.
  • the nanoparticle can, for example, further comprise a capping layer comprising a plurality of ligands.
  • the average particle size of the nanoparticle as measured by transmission electron microscopy can, for example, be from 1 nm to 20 nm (e.g., from 1 nm to 5 nm). In some examples, the number of nanoparticles at least partially encapsulated within each vesicle can be 1 or more (e.g., from 1 to 200).
  • the nanoparticle and the sterol can be present in the composition, for example, in a molar ratio of from 1: 10000 to 1:50 (e.g., from 1:1800 to 1:100).
  • the nanoparticle and the surfactant can be present in the composition in a molar ratio of from 1:10000 to 1:50 (e.g., from 1:1800 to 1:100).
  • the average size of the composite nanocarrrier as measured by dynamic light scattering can, for example, be from 25 to 500 nm (e.g., from 50 nm to 300 nm).
  • compositions described herein can be substantially stable. In some examples, the compositions can be substantially stable upon dilution. In some examples, the average size of the composite nanocarriers can change by 35% or less over a period of time (e.g., 8 weeks or more) and/or upon dilution.
  • the composition can comprise a fluorescent composition.
  • the fluorescence of the composition can be stable upon dilution of the composition.
  • the peak wavelength of the photoluminescence spectrum of the fluorescent composition can shift by 60 nm or less over a period of time (e.g., 12 weeks or more) and/or upon dilution.
  • compositions can, in some examples, be biocompatible. In some examples, the compositions can be stable under physiological conditions.
  • compositions can comprise, in some examples, water and a cosolvent.
  • aqueous solutions can further comprise a cosolvent.
  • cosolvents include, but are not limited to, alcohols (e.g., methanol, ethanol, n-butanol, isopropanol, n-propanol), carboxylic acids (e.g., acetic acid), chloroform, and combinations thereof.
  • the aqueous solutions are substantially free of precipitate.
  • compositions disclosed herein are methods of making the compositions disclosed herein.
  • methods of making the compositions described herein comprising contacting the nanoparticle and the vesicle, thereby forming a mixture; and mixing the mixture, thereby at least partially encapsulating the nanoparticle within the vesicle (e.g., thereby forming the composite nanocarrier).
  • Mixing can be accomplished by mechanical stirring, shaking, vortexing, sonication (e.g., bath sonication, probe sonication), and the like.
  • the mixture is bath sonicated.
  • the mixture can be bath sonicated for from 10 seconds to 5 hours (e.g., from 1 minute to 30 minutes, or for 5 minutes).
  • the method can further comprise forming the vesicle.
  • the method can further comprise forming the nanoparticle.
  • compositions that comprise the compositions disclosed herein in combination with a pharmaceutically acceptable excipient. Also disclosed herein are methods of use of the composition disclosed herein, wherein the composition is used as a sensor to detect the presence or amount of a biological moiety; the structure, composition, and conformation of a biological moiety; the localization of a biological moiety in an environment; interactions of biological moieties; alterations in structures of biological compounds; alterations in biological processes; or combinations thereof.
  • the compositions can further comprise a targeting moiety that has an affinity for a biological target.
  • compositions disclosed herein are methods of use of the compositions disclosed herein in devices.
  • devices comprising the compositions disclosed herein.
  • devices include, but are not limited to, electronic devices, energy storage devices, energy conversion devices (e.g., solar cells, fuel cells, photovoltaic cells), optical devices (e.g., light emitting diodes), optoelectronic devices, bioanalytical devices, chemical sensors, biosensors, and combinations thereof.
  • the methods can comprise administering to the subject an amount of a composition as described herein; and detecting the composition.
  • imaging methods can be used, for example, for assessing the extent of a disease and/or the target of a therapeutic agent.
  • the cells are indicative of a disease, such as cancer.
  • Figure 1 is a transmission electron microscopy (TEM) image of octene-coated silicon nanocrystals used in the silicon nanocrystal and nanovesicle assembly experiments.
  • TEM transmission electron microscopy
  • Figure 2 is a TEM image of octene-coated silicon nanocrystals used in the silicon nanocrystal and nanovesicle assembly experiments.
  • Figure 3 is a TEM image of octene-coated silicon nanocrystals used in the silicon nanocrystal and nanovesicle assembly experiments.
  • Figure 4 is a histogram of a sample of 150 nanocrystals measured from the TEM images of octene-coated silicon nanocrystals used in the silicon nanocrystal and nanovesicle assembly experiments shows the average size of the silicon nanocrystals is 2.8 nm with a standard deviation of 0.6 nm.
  • Figure 5 shows the results of thermogravimetric analysis of silicon nanocrystals coated with octene ligand.
  • Figure 6 is a schematic representation of the process for incorporating silicon nanocrystals into nanovesicles through bath sonication.
  • Figure 7 is a cryo-TEM image of nanovesicles (left) as well as photographs (upper right) of the vial containing the nanovesicles under ambient light (left) and under a 365 nm ultraviolet lamp (right) and a diagram of the nanovesicle structures (lower right).
  • Figure 8 is a TEM image of silicon nanocrystals (left) as well as photographs (upper right) of the vial containing the silicon nanocrystals under ambient light (left) and under a 365 nm ultraviolet lamp (right) and a diagram of the silicon nanocrystal structures (lower right).
  • Figure 9 is a Cryo-TEM images of the nano vesicle-silicon nanocrystal assemblies (left), as well as photographs (upper right) of the vial containing the nanovesicle-silicon nanocrystal assemblies under ambient light (left) and under a 365 nm ultraviolet lamp (right) and a diagrams of the nanovesicle-silicon nanocrystal assemblies (lower right).
  • Figure 10 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for spherical structures of silicon nanocrystals with similar sizes as plain nanovesicles (arrow) and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 11 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for spherical structures of silicon nanocrystals with similar sizes as plain nanovesicles (upper arrow), nanovesicles with silicon nanocrystals on one side (lower arrow), and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 12 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for nanovesicles with silicon nanocrystals on one side (arrows) and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 13 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for spherical structures of silicon nanocrystals with similar sizes as plain nanovesicles (rightmost arrow), nanovesicles with silicon nanocrystals on one side (left two arrows), and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 14 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for nanovesicles with silicon nanocrystals on one side (lower arrow), nanovesicles connected by silicon nanocrystal aggregates (upper arrow), and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 15 is a Cryo-TEM image of fluorescent dispersions of nanovesicles and silicon nanocrystals. Examples are shown for nanovesicles connected by silicon nanocrystal aggregates (arrow) and empty nanovesicles with no silicon nanocrystals incorporated.
  • Figure 16 is a diagram of the radius of an average surface of both membranes (R s ) used to estimate the number of cholesterol-CTAB pairs in a typical nanovesicle.
  • Figure 17 is a diagram of the dimensions of the headgroup of the CTAB surfactant used to estimate the number of cholesterol and CTAB molecules per nanovesicles.
  • Figure 18 is a normalized absorbance (solid lines), PL (320 nm excitation) (dashed lines), and PLE (660 nm emission for silicon nanocrystal in chloroform, 670 nm emission for silicon nanocrystal in nanovesicles) (dotted lines) spectra for octene coated silicon nanocrystals dispersed in chloroform or incorporated into nanovesicles in an aqueous media.
  • Figure 19 shows photographs of vials of silicon nanocrystals incorporated into nanovesicles and control solutions under ambient light (top) and under a 365 nm UV lamp (bottom) taken immediately after preparation.
  • the five vials monitored were (i) silicon nanocrystals in 7 mM cholesterol-CTAB nanovesicles (with CTAB concentration above cmc),
  • Figure 20 shows photographs of vials of silicon nanocrystals incorporated into nanovesicles and control solutions under ambient light (top) and under a 365 nm UV lamp (bottom) taken one day after preparation.
  • the five vials monitored were (i) silicon nanocrystals in 7 mM cholesterol-CTAB nanovesicles (with CTAB concentration above cmc), (ii) silicon nanocrystals in 0.7 mM cholesterol-CTAB nanovesicles (with CTAB concentration bellow cmc),
  • the five vials monitored were (i) silicon nanocrystals in 7 mM cholesterol-CTAB nanovesicles (with CTAB concentration above cmc), (ii) silicon nanocrystals in 0.7 mM cholesterol-CTAB nanovesicles (with CTAB concentration bellow cmc), (iii) silicon nanocrystals in 7 mM CTAB micelles, (iv) silicon nanocrystals in 10% EtOH, and (v) chloroform in 7 mM CTAB nanovesicles. Vials were prepared by adding 20 ⁇ silicon nanocrystal (in chloroform) to 0.75 ml of solution, and then bath sonicated for 5 minutes.
  • Figure 22 shows photographs of vials of silicon nanocrystals incorporated into nanovesicles and control solutions under ambient light (top) and under a 365 nm UV lamp
  • the five vials monitored were (i) silicon nanocrystals in 7 mM cholesterol-CTAB nanovesicles (with CTAB concentration above cmc), (ii) silicon nanocrystals in 0.7 mM cholesterol-CTAB nanovesicles (with CTAB concentration bellow cmc), (iii) silicon nanocrystals in 7 mM CTAB micelles, (iv) silicon nanocrystals in 10% EtOH, and (v) chloroform in 7 mM CTAB nanovesicles. Vials were prepared by adding 20 ⁇ silicon nanocrystal (in chloroform) to 0.75 ml of solution, and then bath sonicated for 5 minutes.
  • Figure 23 shows photographs of vials of silicon nanocrystals incorporated into nanovesicles and control solutions under ambient light (top) and under a 365 nm UV lamp (bottom) taken 12 weeks after preparation.
  • the five vials monitored were (i) silicon nanocrystals in 7 mM cholesterol-CTAB nanovesicles (with CTAB concentration above cmc), (ii) silicon nanocrystals in 0.7 mM cholesterol-CTAB nanovesicles (with CTAB concentration bellow cmc), (iii) silicon nanocrystals in 7 mM CTAB micelles, (iv) silicon nanocrystals in 10% EtOH, and (v) chloroform in 7 mM CTAB nanovesicles.
  • Vials were prepared by adding 20 ⁇ silicon nanocrystal (in chloroform) to 0.75 ml of solution, and then bath sonicated for 5 minutes.
  • Figure 24 shows the absorbance measured at 320 nm for samples with silicon
  • nanocrystals demonstrate the stability of the nanoparticle fluorescence in nanovesicles.
  • Figure 25 shows the average PL wavelength for samples with silicon nanocrystals (excited at 320 nm) demonstrate the stability of the nanoparticle fluorescence in nanovesicles.
  • Figure 26 is a Cryo-TEM image of silicon nanocrystals in low concentration of nanovesicles (below CMC). 0.75 ml of 0.7 mM cholesterol-CTAB nanovesicles was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals in chloroform, and the mixture was bath sonicated for 5 minutes.
  • Figure 27 is a Cryo-TEM image of silicon nanocrystals in low concentration of nanovesicles (below CMC). 0.75 ml of 0.7 mM cholesterol-CTAB nanovesicles was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals in chloroform, and the mixture was bath sonicated for 5 minutes.
  • Figure 28 is a Cryo-TEM image of silicon nanocrystals in low concentration of nanovesicles (below CMC). 0.75 ml of 0.7 mM cholesterol-CTAB nanovesicles was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals in chloroform, and the mixture was bath sonicated for 5 minutes.
  • Figure 29 is a Cryo-TEM image of silicon nanocrystals in low concentration of nanovesicles (below CMC). 0.75 ml of 0.7 mM cholesterol-CTAB nanovesicles was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals in chloroform, and the mixture was bath sonicated for 5 minutes.
  • Figure 30 is a Cryo-TEM image taken on the day the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 31 is a Cryo-TEM image taken on the day the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 32 is a Cryo-TEM image taken on the day the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 33 is a Cryo-TEM image taken 2 days after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 34 is a Cryo-TEM image taken 2 days after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 35 is a Cryo-TEM image taken 2 days after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 36 is a Cryo-TEM image taken 7 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 37 is a Cryo-TEM image taken 7 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 38 is a Cryo-TEM image taken 7 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 39 is a Cryo-TEM image taken 12 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 40 is a Cryo-TEM image taken 12 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 41 is a Cryo-TEM image taken 12 weeks after the sample was prepared of the structures observed after incorporation of silicon nanocrystals into nanovesicles (7 mM cholesterol-CTAB) through 5 minutes of bath sonication.
  • Figure 42 is a Cryo-TEM image of CTAB stabilized silicon nanocrystals. 0.75 ml of 7 mM CTAB micelles in water was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals (in chloroform), and the mixture was bath sonicated for 5 minutes.
  • Figure 43 is a Cryo-TEM image of CTAB stabilized silicon nanocrystals. 0.75 ml of 7 mM CTAB micelles in water was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals (in chloroform), and the mixture was bath sonicated for 5 minutes.
  • Figure 44 is a Cryo-TEM image of CTAB stabilized silicon nanocrystals. 0.75 ml of 7 mM CTAB micelles in water was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals (in chloroform), and the mixture was bath sonicated for 5 minutes.
  • Figure 45 is a Cryo-TEM image of CTAB stabilized silicon nanocrystals. 0.75 ml of 7 mM CTAB micelles in water was combined with 20 ⁇ of 6.75 mg/ml silicon nanocrystals (in chloroform), and the mixture was bath sonicated for 5 minutes.
  • Figure 46 shows the size distribution of 20 ⁇ of silicon nanocrystals in chloroform incorporated into 750 ⁇ nanovesicles (sample (i) from stability trials), measured by dynamic light scattering (DLS), following 5 minutes of bath sonication. Measurements were done in week 0 and in week 8. Sizes measured by DLS (each measured in triplicate) were: a z-ave of 54.34 nm with a polydispersity index (PDI) of 0.262 at week 0; and a z-ave of 65.17 nm with a PDI of 0.157 at week 8.
  • PDI polydispersity index
  • Figure 47 shows the size distribution of 20 ⁇ of chloroform with 750 ⁇ nanovesicles (sample (v) from stability trials), measured by DLS, following 5 minutes of bath sonication. Measurements were done in week 0 and in week 8. Sizes measured by DLS (each measured in triplicate) were: a z-ave of 58.43 nm with a PDI of 0.235 at week 0; and a z-ave of 79.34 nm with a PDI of 0.096 at week 0.
  • Figure 48 is a Cryo-TEM image showing incorporation of silicon nanocrystals into nanovesicles formed with only water (no ethanol).
  • Figure 49 is a Cryo-TEM image showing incorporation of silicon nanocrystals into nanovesicles formed with only water (no ethanol).
  • Figure 50 is a Cryo-TEM image showing incorporation of silicon nanocrystals into nanovesicles formed with only water (no ethanol).
  • Figure 51 shows photographs of vials containing the samples formed by incorporating silicon nanocrystals into nanovesicles formed with only water (no ethanol) under ambient light (left) and under a 366 nm ultraviolet lamp (right), showing the characteristic fluorescence from the silicon nanocrystals.
  • Figure 52 is a Cryo-TEM image of the sample bath sonicated for 1 minute to incorporate silicon nanocrystals into nanovesicles.
  • Figure 53 is a Cryo-TEM image of the sample bath sonicated for 5 minutes to incorporate silicon nanocrystals into nanovesicles.
  • Figure 54 is a Cryo-TEM image of the sample bath sonicated for 15 minutes to incorporate silicon nanocrystals into nanovesicles.
  • Figure 55 is a Cryo-TEM image of the sample bath sonicated for 30 minutes to incorporate silicon nanocrystals into nanovesicles.
  • Figure 56 shows the dynamic light scattering (DLS) data results from using different bath sonication times to incorporate silicon nanocrystals into nanovesicles showed that at the longer time points of 15 and 30 minutes, nanovesicles appear smaller in size.
  • Sizes measured by DLS were: a z-ave of 82.44 nm with a PDI of 0.248 at 1 min; a z-ave of 69.02 nm with a PDI of 0.232 at 5 min; a z-ave of 60.71 nm with a PDI of 0.154 at 15 min; and a z-ave of 64.61 nm with a PDI of 0.139 at 30 min.
  • Figure 57 shows the results from preparing DOPC (neutral) liposomes separately and then adding 20 ⁇ silicon nanocrystals in chloroform and bath sonicating for 5 minutes.
  • Photographs of vials of DOPC were taken under ambient light (top row) and under a 365 nm UV lamp (bottom row) (i) before bath sonication, (ii) immediately after sonication, (iii) after 1 day, and (iv) after 3 days, showing that DOPC precipitated out of solution.
  • Figure 58 is a Cryo-TEM image of the DOPC liposomes before adding nanocrystals showed that the DOPC liposomes formed small unilamellar vesicles.
  • Figure 59 is a Cryo-TEM image of the DOPC liposomes after bath sonication showed that silicon nanocrystals incorporated with the lipid and formed large complexes.
  • Figure 60 is a Cryo-TEM image of the DOPC liposomes after bath sonication showed that silicon nanocrystals incorporated with the lipid and formed large complexes.
  • Figure 61 shows the results from preparing DOPG (anionic) liposomes separately and then adding 20 ⁇ silicon nanocrystals in chloroform and bath sonicating for 5 minutes.
  • Photographs of vials of the DOPG sample were taken under ambient light (upper row) and under a 365 nm UV lamp (bottom row) (i) before bath sonication, (ii) immediately after sonication, (iii) after 1 day, and (iv) after 3 days, showing that the DOPG solution remained turbid.
  • Figure 62 is a Cryo-TEM image of the DOPG liposomes before adding nanocrystals showed that the DOPG liposomes formed small unilamellar vesicles.
  • Figure 63 is a Cryo-TEM image of the DOPG liposomes after bath sonication showed that the silicon nanocrystals aggregated outside of empty liposomes, and no incorporation with the liposomes was observed.
  • Figure 64 is a Cryo-TEM image of the DOPG liposomes after bath sonication showed that the silicon nanocrystals aggregated outside of empty liposomes, and no incorporation with the liposomes was observed.
  • Figure 65 shows photographs of vials containing (i) 7 mM CTAB micelles and (ii) 7 mM cholesterol-CTAB nanovesicles one day after preparation with 5 minutes of bath sonication, prior to addition into dialysis tubing, under ambient light (top) and on 254 nm UV lamp (bottom).
  • Figure 66 shows photographs of dialysis tubing with solutions containing (i) 7 mM CTAB micelles and (ii) 7 mM cholesterol-CTAB nanovesicles after 1 round of dialysis, under ambient light (top) and under a 254 nm UV lamp (bottom).
  • Figure 67 shows photographs of dialysis tubing with solutions containing (i) 7 mM CTAB micelles and (ii) 7 mM cholesterol-CTAB nanovesicles after 3 rounds of dialysis, under ambient light (top) and under a 254 nm UV lamp (bottom).
  • Figure 68 shows photographs of dialysis tubing with solutions containing (i) 7 mM
  • CTAB micelles and (ii) 7 mM cholesterol-CTAB nanovesicles after 6 rounds of dialysis, under ambient light (top) and under a 254 nm UV lamp (bottom).
  • Figure 69 shows photographs of solutions (i) 7 mM CTAB micelles or (ii) 7 mM cholesterol-CTAB nanovesicles removed from dialysis tubing after 6 rounds of dialysis, under ambient light (top) and on 254 nm UV lamp (bottom).
  • Figure 70 is a Cryo-TEM image of sample with cholesterol-CTAB nanovesicles and silicon nanocrystals following 6 rounds of dialysis.
  • Figure 71 is a Cryo-TEM image of sample with cholesterol-CTAB nanovesicles and silicon nanocrystals following 6 rounds of dialysis.
  • Figure 72 is a Cryo-TEM image of sample with cholesterol-CTAB nanovesicles and silicon nanocrystals following 6 rounds of dialysis.
  • Figure 73 is a Cryo-TEM image of sample with cholesterol-CTAB nanovesicles and silicon nanocrystals following 6 rounds of dialysis.
  • Figure 74 shows photographs of samples prepared by adding different volume ratios of silicon nanocrystals (in chloroform) : Nanovesicles (in water), under ambient light (top row) and under a 254 nm UV lamp (bottom row) before sonication. In each sample 135 ⁇ g of silicon nanocrystals was added, though in different concentrations, and thus volumes.
  • Samples from left to right are: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • Figure 75 shows photographs of sample prepared by adding different volume ratios of silicon nanocrystals (in chloroform) : Nanovesicles (in water), under ambient light (top row) and under a 254 nm UV lamp (bottom row), immediately after sonication. In each sample 135 ⁇ g of silicon nanocrystals was added, though in different concentrations, and thus volumes.
  • Samples from left to right are: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • Figure 76 shows photographs of samples prepared by adding different volume ratios of silicon nanocrystals (in chloroform) : Nanovesicles (in water), under ambient light (top row) and under a 254 nm UV lamp (bottom row), 1 day after sonication. In each sample 135 ⁇ g of silicon nanocrystals was added, though in different concentrations, and thus volumes.
  • Samples from left to right are: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • Figure 77 shows photographs of samples prepared by adding different volume ratios of silicon nanocrystals (in chloroform) : Nanovesicles (in water), under ambient light (top row) and under a 254 nm UV lamp (bottom row), 1 week after sonication. In each sample 135 ⁇ g of silicon nanocrystals was added, though in different concentrations, and thus volumes.
  • Samples from left to right are: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • Figure 78 shows photographs of samples prepared by adding different volume ratios of silicon nanocrystals (in chloroform) : Nanovesicles (in water), under ambient light (top row) and under a 254 nm UV lamp (bottom row) 6 weeks after sonication. In each sample 135 ⁇ g of silicon nanocrystals was added, though in different concentrations, and thus volumes.
  • Samples from left to right are: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • Figure 79 shows photographs of sample prepared by adding 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform under ambient light 1 day after sonication, showing an orange-brown precipitate consistent with silicon nanocrystals.
  • Figure 80 shows photographs of vial under 365 nm UV light of sample that was probe sonicated for 3 minutes to incorporate silicon nanocrystals into nanovesicles. The photographs show precipitation from solution and loss of fluorescence: (i) immediately after sonication, (ii) 1 day after preparation, and (iii) 1.5 months after preparation.
  • Figure 81 shows photographs of samples prepared using (i) 5 minute bath sonication to
  • Figure 82 shows photographs of samples prepared using (i) 5 minute bath sonication to
  • Figure 83 is a Cryo-TEM image of the sample that used vortexing to incorporate silicon nanocrystals into the nanovesicles showed no silicon nanocrystals incorporated into the nanovesicles.
  • Figure 84 is a Cryo-TEM image of the sample that used vortexing to incorporate silicon nanocrystals into the nanovesicles showed no silicon nanocrystals incorporated into the nanovesicles.
  • Figure 85 shows the DLS data for silicon nanocrystals incorporated into the nanovesicles via bath sonication or vortexing indicated that vortexing changed the size distribution. Sizes measured by DLS (each measured in triplicate) were: a z-average of 108.4 nm with a PDI of 0.168 for bath sonication; and a z-average of 71.58 nm with a PDI of 0.214 for vortexing.
  • Figure 86 is a schematic diagram of the interactions of silicon particles and nanovesicles, and the formation of the stable silicon nanocrystal covered with a monolayer of nanovesicle.
  • Figure 87 is a schematic representation of the process of the formation of the silicon nanocrystal-nanovesicle assemblies, their long term structural stability, and long term fluorescence stability.
  • compositions and methods described herein may be understood more readily by reference to the following detailed description of specific aspects of the disclosed subject matter and the Examples and Figures included therein.
  • a composition includes mixtures of two or more such compositions
  • the vesicle includes mixtures of two or more such vesicles
  • reference to “a nanoparticle” includes mixture of two or more such nanoparticles, and the like.
  • Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. By “about” is meant within 5% of the value, e.g., within 4, 3, 2, or 1 % of the value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as
  • a “subject” is meant an individual.
  • the "subject” can include domesticated animals (e.g. , cats, dogs, etc.), livestock (e.g. , cattle, horses, pigs, sheep, goats, etc.), laboratory animals (e.g. , mouse, rabbit, rat, guinea pig, etc.), and birds.
  • “Subject” can also include a mammal, such as a primate or a human.
  • the subject can be a human or veterinary patient.
  • patient refers to a subject under the treatment of a clinician, e.g., physician.
  • pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio.
  • compositions comprising an aqueous solution comprising a composite nanocarrier, the composite nanocarrier comprising a nanoparticle at least partially encapsulated within a vesicle.
  • the vesicle can have an average size.
  • Average size and “mean size” are used interchangeably herein with respect to the vesicles, and generally refer to the Z-average particle size of a population of vesicles as measured by dynamic light scattering (DLS).
  • DLS dynamic light scattering
  • the average size for a plurality of vesicles with a substantially spherical shape can comprise the average diameter of the plurality of vesicles as measured by dynamic light scattering.
  • the vesicle can have an average size of 25 nanometers (nm) or more as measured by dynamic light scattering (e.g., 30 nm or more, 35 nm or more, 40 nm or more, 45 nm or more, 50 nm or more, 55 nm or more, 60 nm or more, 65 nm or more, 70 nm or more, 75 nm or more, 80 nm or more, 85 nm or more, 90 nm or more, 95 nm or more, 100 nm or more, 110 nm or more, 120 nm or more, 130 nm or more, 140 nm or more, 150 nm or more, 160 nm or more, 170 nm or more, 180 nm or more, 190 nm or more, 200 nm or more, 210 nm or more, 220 nm or more, 230 nm or more, 240 nm or more, 250 nm or more,
  • the vesicle can have an average size of 500 nm or less as measured by dynamic light scattering (e.g., 475 nm or less, 450 nm or less, 425 nm or less, 400 nm or less, 375 nm or less, 350 nm or less, 325 nm or less, 300 nm or less, 290 nm or less, 280 nm or less, 270 nm or less, 260 nm or less, 250 nm or less, 240 nm or less, 230 nm or less, 220 nm or less, 210 nm or less, 200 nm or less, 190 nm or less, 180 nm or less, 170 nm or less, 160 nm or less, 150 nm or less, 140 nm or less, 130 nm or less, 120 nm or less, 110 nm or less, 100 nm or less, 95 nm or less, 90 nm or
  • the average size of the vesicle as measured by dynamic light scattering can range from any of the minimum values described above to any of the maximum values described above.
  • the vesicle can have an average size of from 25 to 500 nm as measured by dynamic light scattering (e.g., from 25 nm to 250 nm, from 250 nm to 500 nm, from 25 nm to 100 nm, from 100 nm to 200 nm, from 200 nm to 300 nm, from 300 nm to 400 nm, from 400 nm to 500 nm, from 30 nm to 450 nm, from 35 nm to 400 nm, from 40 nm to 350 nm, or from 50 nm to 300 nm).
  • the vesicle can comprise a plurality of vesicles that can be substantially monodisperse.
  • a monodisperse distribution of vesicles refers to vesicle distributions in which the polydispersity index (PDI) as measured by dynamic light scattering is 0.35 or less (e.g., 0.30 or less, 0.25 or less, 0.20 or less, 0.15 or less, 0.10 or less, or 0.05 or less).
  • PDI polydispersity index
  • the vesicle can be substantially spherical in shape.
  • substantially spherical in shape can include spherical, elliptical, ovular, or any other spheroidal shape.
  • the vesicle can comprise a sterol and a surfactant.
  • the vesicle can, for example, be formed by self-assembly of the sterol and the surfactant.
  • a lipid is not a surfactant, such that the vesicles are not liposomes.
  • Suitable surfactants can be anionic, cationic, amphoteric, or nonionic surface active agents. Suitable anionic surfactants include, but are not limited to, those containing carboxylate, sulfonate and sulfate ions.
  • anionic surfactants include sodium, potassium, ammonium of long chain alkyl sulfonates and alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate; dialkyl sodium sulfosuccinates, such as sodium dodecylbenzene sulfonate; dialkyl sodium sulfosuccinates, such as sodium bis-(2- ethylthioxyl)-sulfosuccinate; and alkyl sulfates such as sodium lauryl sulfate.
  • nonionic surfactants include ethylene glycol monostearate, propylene glycol myristate, glyceryl monostearate, glyceryl stearate, polyglyceryl-4-oleate, sorbitan acylate, sucrose acylate, PEG- 150 laurate, PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbates,
  • polyoxy ethylene octylphenylether PEG- 1000 cetyl ether, polyoxyethylene tridecyl ether, polypropylene glycol butyl ether, Poloxamer® 401, stearoyl monoisopropanolamide, and polyoxyethylene hydrogenated tallow amide.
  • amphoteric surfactants include sodium N-dodecyl- -alanine, sodium N-lauryl- -iminodipropionate, myristoamphoacetate, lauryl betaine and lauryl sulfobetaine.
  • Cationic surfactants include, but are not limited to, quaternary ammonium surfactants.
  • quaternary ammonium surfactants are quaternary ammonium salts in which at least one nitrogen substituent is a long chain alkyl group.
  • quaternary ammonium surfactants include, but are not limited to, cetyl trimethylammonium bromide (CTAB), cetyl trimethylammonium chloride (CTAC), cetylpyridinium chloride (CPC), benzalkonium chloride (BAC), menzethonium chloride (BZT), myristalkonium chloride (MKC), 5-bromo-5-nitro-l,3- dioxane, dimethyldioctadecylammonium chloride, dioctadecylmethylammonium bromide (DODAB), and combinations thereof.
  • CTAB cetyl trimethylammonium bromide
  • CTC cetyl trimethylammonium chloride
  • CPC cetylpyridinium chloride
  • BAC benzalkonium chloride
  • BZT menzethonium chloride
  • MKC myristalkonium chloride
  • DODAB dioctadecylmethylammonium bromide
  • the vesicle comprises a sterol and a quaternary ammonium surfactant. In some examples, the vesicle consists of a sterol and a quaternary ammonium surfactant.
  • sterols include, but are not limited to, adosterol, avenasterol, azacosterol, blazein, campesterol, cerevisterol, cholesterol, cycloartenol, dinosterol, episterol, ergosterol, fecosterol, fucosterol, fungisterol, ganoderiol, anodermadiol, gandoderenic acid, inotodiol, lanosterol, lathosterol, lichesterol, lucidadiol, lumisterol, sitosterol, spinasterol, stigmasterol, trametenolic acid, zhankuid acid, derivatives thereof, and combinations thereof.
  • the sterol comprises cholesterol or a derivative thereof.
  • the sterol consists of cholesterol or a derivative thereof.
  • the sterol and the surfactant can be present in the vesicle in a molar ratio of 10:1 or less (e.g., 9.5:1 or less, 9:1 or less, 8.5:1 or less, 8:1 or less, 7.5:1 or less, 7: 1 or less, 6.5: 1 or less, 6: 1 or less, 5.5:1 or less, 5: 1 or less, 4.5:1 or less, 4: 1 or less, 3.5:1 or less, 3:1 or less, 2.5:1 or less, 2: 1 or less, 1.9:1 or less, 1.8:1 or less, 1.7: 1 or less, 1.6: 1 or less, 1.5:1 or less, 1.4: 1 or less, 1.3:1 or less, 1.2:1 or less, 1.1:1 or less, 1:1 or less, 1:1.1 or less, 1:1.2 or less, 1:1.3 or less, 1: 1.4 or less, 1:1.5 or less, 1:1.6 or less, 1:1.7 or less, 1:1.8
  • the sterol and the surfactant can be present in the vesicle in a molar ratio of 1:5 or more (e.g., 1:4.5 or more, 1:4 or more, 1:3.5 or more, 1:3 or more, 1:2.5 or more, 1:2 or more, 1:1.9 or more, 1:1.8 or more, 1: 1.7 or more, 1:1.6 or more, 1: 1.5 or more, 1:1.4 or more, 1 : 1.3 or more, 1 : 1.2 or more, 1:1.1 or more, 1 : 1 or more, 1.1 : 1 or more, 1.2:1 or more,
  • the molar ratio of the sterol and the surfactant present in the vesicle can range from any of the minimum values described above to any of the maximum values described above.
  • the sterol and the surfactant can be present in the vesicle in a molar ratio of from 10: 1 to 1:5 (e.g., from 10:1 to 1:1, from 1: 1 to 1:5, from 5:1 to 1:5, from 4:1 to 1:4, from 3: 1 to 1:3, from 2:1 to 1:2, or from 1.5:1 to 1:1.5).
  • the sterol and the surfactant can be present in the vesicle in a molar ratio of 1 : 1.
  • the nanoparticle that can be used in the compositions disclosed herein can comprise, for example, a semiconductor.
  • the nanoparticle can include a semiconductor that comprises a wide band gap.
  • the band gap can be greater than 1 eV.
  • the band gap can be an indirect band gap.
  • the nanoparticle can comprise a semiconductor such as Fe203, WO3, Ta3N 5 , TaON, T1O2, ZnO, CdS, CdSe, Si, or combinations thereof.
  • the nanoparticle can comprise Si.
  • the nanoparticle can comprise a nanocrystal.
  • the nanocrystal can comprise Si.
  • the nanoparticle that can be used in the compositions disclosed herein can comprise, for example, a metal.
  • the nanoparticle can comprise a metal selected from the group consisting of Be, Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, In, Sn, Ba, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and combinations thereof.
  • the nanoparticle can comprise a magnetic nanoparticle.
  • the magnetic nanoparticle can comprise any suitable material, for example Fe, Co, Zn, Ni, Mn, Ag, Au, C, Cd, or a combination thereof.
  • the magnetic nanoparticle can comprise any suitable metal compound, such as an oxide of Fe, Co, Zn, Ni, Mn, or a combination thereof.
  • the magnetic nanoparticle comprise an iron oxide, for example Fe30 4 .
  • the nanoparticle that can be used in the compositions disclosed herein can be capable of absorbing energy of a first wavelength.
  • the nanoparticle e.g., size, shape, composition
  • the nanoparticle can comprise a plasmonic nanoparticle.
  • the plasmonic nanoparticle can any suitable material, for example Au, Ag, Pd, and combinations thereof.
  • the nanoparticle can be capable of absorbing energy of a first wavelength and emitting electromagnetic radiation (such as near infrared and visible light).
  • the nanoparticle can comprise a fluorescent nanoparticle.
  • the optical properties can be, for example, a function of both the nanoparticle composition and physical size. Both the absorption and the photoluminescent wavelength are a function of the nanoparticle size and composition.
  • the nanoparticle size, shape, and/or composition can, for example, be selected to tune the fluorescent properties of the composition.
  • the nanoparticle can be biocompatible, such that the system is suitable for use in a variety of biological applications.
  • Biocompatible or “biologically compatible”, as used herein, generally refer to compounds or particles that are, along with any metabolites or degradation products thereof, generally non-toxic to cells and tissues, and which do not cause any significant adverse effects to cells and tissues when cells and tissues are incubated (e.g. , cultured) in their presence.
  • the biocompatible nanoparticle can be degradable.
  • the biocompatible nanoparticle can be inert, that is, stable in biological environments.
  • the nanoparticle can be coated with a biocompatible material.
  • the biocompatible material can be a lipid, a carbohydrate, a polysaccharide, a protein, an antibody, a glycoprotein, a glycolipid, silica, alumina, titanium oxide or combinations thereof.
  • a suitable biocompatible nanoparticle include a silicon containing nanoparticle.
  • the nanoparticle can have an average particle size.
  • Average particle size “Average particle size,” “mean particle size,” and “median particle size” are used interchangeably herein with respect to the nanoparticles, and generally refer to the statistical mean particle size of the nanoparticles in a population of nanoparticles.
  • the average particle size for a plurality of nanoparticles with a substantially spherical shape can comprise the average diameter of the plurality of nanoparticles.
  • Mean particle size can be measured using methods known in the art, such as evaluation by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and/or small angle X-ray scattering (SAXS).
  • the nanoparticle can, for example, have an average particle size that is less than the average particle size of the vesicle.
  • the nanoparticle can have an average particle size of 1 nm or more as measured by transmission electron microscopy (e.g., 2 nm or more, 3 nm or more, 4 nm or more, 5 nm or more, 6 nm or more, 7 nm or more, 8 nm or more, 9 nm or more, 10 nm or more, 11 nm or more, 12 nm or more, 13 nm or more, 14 nm or more, 15 nm or more, 16 nm or more, 17 nm or more, 18 nm or more, or 19 nm or more).
  • the nanoparticle can have an average particle size of 20 nm or less as measured by transmission electron microscopy (e.g., 19 nm or less, 18 nm or less, 17 nm or less, 16 nm or less, 15 nm or less, 14 nm or less, 13 nm or less, 12 nm or less, 11 nm or less, 10 nm or less, 9 nm or less, 8 nm or less, 7 nm or less, 6 nm or less, 5 nm or less, 4 nm or less, 3 nm or less, or 2 nm or less).
  • transmission electron microscopy e.g., 19 nm or less, 18 nm or less, 17 nm or less, 16 nm or less, 15 nm or less, 14 nm or less, 13 nm or less, 12 nm or less, 11 nm or less, 10 nm or less, 9 nm or less, 8 nm or less
  • the average particle size of the nanoparticle as measured by transmission electron microscopy can range from any of the minimum values described above to any of the maximum values described above.
  • the nanoparticle can have an average particle size of from 1 nm to 20 nm as measured by transmission electron microscopy (e.g., from 1 nm to 10 nm, from 10 nm to 20 nm, from 1 nm to 5 nm, from 5 nm to 10 nm, from 10 nm to 15 nm, from 15 nm to 20 nm, or from 5 nm to 15 nm).
  • the nanoparticle can comprise a plurality of nanoparticles that can be substantially monodisperse.
  • a monodisperse distribution refers to nanoparticles distributions in which 70% of the distribution (e.g., 75% of the distribution, 80% of the distribution, 85% of the distribution, 90% of the distribution, or 95% of the distribution) lies within 25% of the median particle size (e.g., within 20% of the median particle size, within 15% of the median particle size, within 10% of the median particle size, or within 5% of the median particle size).
  • the nanoparticle can be of any shape (e.g., sphere, rod, cube, rectangle, octahedron, truncated octahedron, plate, cone, prism, ellipse, triangle, etc.).
  • the nanoparticle can be substantially spherical in shape.
  • the nanoparticle can comprise a core-shell nanoparticle.
  • the nanoparticle can, for example, further comprise a capping layer comprising a plurality of ligands.
  • a capping layer comprising a plurality of ligands.
  • Suitable ligands for capping layers for nanoparticles are known in the art.
  • the ligands can be attached to the nanoparticle, for example, by coordination bonds. Ligands can also be associated with the nanoparticle via non-covalent interactions. In some examples, the ligands can individually be selected to be a hydrophilic, hydrophobic, or amphiphilic. In addition, the plurality of ligands can, in combination, be selected so as to provide a shell surrounding the nanoparticle which is hydrophilic, hydrophobic, or amphiphilic.
  • the ligands can comprise coordinating or bonding functional groups, such as thiol, amine, phosphine, CO, N 2 , alkene, chloride, hydride, alkyl, and derivatives thereof, and combinations thereof.
  • the nanoparticle and the sterol can be present in the composition, for example, in a molar ratio of 1:10000 or more (e.g., 1:9000 or more, 1:8000 or more, 1:7000 or more, 1:6000 or more, 1:5000 or more, 1:4000 or more, 1:3000 or more, 1:2000 or more, 1:1500 or more, 1:1000 or more, 1:500 or more, or 1:100 or more).
  • 1:10000 or more e.g., 1:9000 or more, 1:8000 or more, 1:7000 or more, 1:6000 or more, 1:5000 or more, 1:4000 or more, 1:3000 or more, 1:2000 or more, 1:1500 or more, 1:1000 or more, 1:500 or more, or 1:100 or more.
  • the nanoparticle and the sterol can be present in the composition in a molar ratio of 1:50 or less (e.g., 1:100 or less, 1:500 or less, 1:1000 or less, 1:1500 or less, 1:2000 or less, 1:3000 or less, 1:4000 or less, 1:5000 or less, 1:6000 or less, 1:7000 or less, 1:8000 or less, or 1:9000 or less).
  • 1:50 or less e.g., 1:100 or less, 1:500 or less, 1:1000 or less, 1:1500 or less, 1:2000 or less, 1:3000 or less, 1:4000 or less, 1:5000 or less, 1:6000 or less, 1:7000 or less, 1:8000 or less, or 1:9000 or less.
  • the molar ratio at which the nanoparticle and the sterol are present in the composition can range from any of the minimum values described above to any of the maximum values described above.
  • the nanoparticle and the sterol can be present in the composition in a molar ratio of from 1: 10000 to 1:50 (e.g., from 1:10000 to 1:5000, from 1:5000 to 1:50, from 1:10000 to 1:8000, from 1:8000 to 1:6000, from 1:6000 to 1:4000, from 1:4000 to 1:2000, from 1:2000 to 1:50, or from 1:1800 to 1:100).
  • the nanoparticle and the surfactant can be present in the composition in a molar ratio of 1:10000 or more (e.g., 1:9000 or more, 1:8000 or more, 1:7000 or more, 1:6000 or more, 1:5000 or more, 1:4000 or more, 1:3000 or more, 1:2000 or more, 1:1500 or more, 1:1000 or more, 1:500 or more, or 1:100 or more).
  • 1:10000 or more e.g., 1:9000 or more, 1:8000 or more, 1:7000 or more, 1:6000 or more, 1:5000 or more, 1:4000 or more, 1:3000 or more, 1:2000 or more, 1:1500 or more, 1:1000 or more, 1:500 or more, or 1:100 or more.
  • the nanoparticle and the surfactant can be present in the composition in a molar ratio of 1:50 or less (e.g., 1:100 or less, 1:500 or less, 1:1000 or less, 1:1500 or less, 1:2000 or less, 1:3000 or less, 1:4000 or less, 1:5000 or less, 1:6000 or less, 1:7000 or less, 1:8000 or less, or 1:9000 or less).
  • 1:50 or less e.g., 1:100 or less, 1:500 or less, 1:1000 or less, 1:1500 or less, 1:2000 or less, 1:3000 or less, 1:4000 or less, 1:5000 or less, 1:6000 or less, 1:7000 or less, 1:8000 or less, or 1:9000 or less.
  • the molar ratio at which the nanoparticle and the surfactant are present in the composition can range from any of the minimum values described above to any of the maximum values described above.
  • the nanoparticle and the surfactant can be present in the composition in a molar ratio of from 1:10000 to 1:50 (e.g., from 1: 10000 to 1:5000, from 1:5000 to 1:50, from 1:10000 to 1:8000, from 1:8000 to 1:6000, from 1:6000 to 1:4000, from 1:4000 to 1:2000, from 1:2000 to 1:50, or from 1:1800 to 1:100).
  • the number of nanoparticles at least partially encapsulated within each vesicle can be 1 or more (e.g., 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 15 or more, 20 or more, 25 or more, 30 or more, 35 or more, 40 or more, 45 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or more, 100 or more, 125 or more, 150 or more, 175 or more, or 200 or more).
  • 1 or more e.g., 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 15 or more, 20 or more, 25 or more, 30 or more, 35 or more, 40 or more, 45 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or more, 100 or more, 125 or more, 150 or more, 175 or more, or 200
  • the composite nanocarrier can have an average size.
  • Average size and “mean size” are used interchangeably herein with respect to the composite nanocarriers, and generally refer to the Z-average particle size of a population of composite nanocarriers as measured by dynamic light scattering.
  • the average size for a plurality of composite nanocarriers with a substantially spherical shape can comprise the average diameter of the plurality of composite nanocarriers as measured by dynamic light scattering.
  • the composite nanocarrier can have an average size of 25 nanometers (nm) or more as measured by dynamic light scattering (e.g., 30 nm or more, 35 nm or more, 40 nm or more, 45 nm or more, 50 nm or more, 55 nm or more, 60 nm or more, 65 nm or more, 70 nm or more, 75 nm or more, 80 nm or more, 85 nm or more, 90 nm or more, 95 nm or more, 100 nm or more, 110 nm or more, 120 nm or more, 130 nm or more, 140 nm or more, 150 nm or more, 160 nm or more, 170 nm or more, 180 nm or more, 190 nm or more, 200 nm or more, 210 nm or more, 220 nm or more, 230 nm or more, 240 nm or more, 250 nm or more,
  • the composite nanocarrier can have an average size of 500 nm or less as measured by dynamic light scattering (e.g., 475 nm or less, 450 nm or less, 425 nm or less, 400 nm or less, 375 nm or less, 350 nm or less, 325 nm or less, 300 nm or less, 290 nm or less, 280 nm or less, 270 nm or less, 260 nm or less, 250 nm or less, 240 nm or less, 230 nm or less, 220 nm or less, 210 nm or less, 200 nm or less, 190 nm or less, 180 nm or less, 170 nm or less, 160 nm or less, 150 nm or less, 140 nm or less, 130 nm or less, 120 nm or less, 110 nm or less, 100 nm or less, 95 nm or less, 90 n
  • the average size of the composite nanocarrrier as measured by dynamic light scattering can range from any of the minimum values described above to any of the maximum values described above.
  • the composite nanocarrier can have an average size of from 25 to 500 nm as measured by dynamic light scattering (e.g., from 25 nm to 250 nm, from 250 nm to 500 nm, from 25 nm to 100 nm, from 100 nm to 200 nm, from 200 nm to 300 nm, from 300 nm to 400 nm, from 400 nm to 500 nm, from 30 nm to 450 nm, from 35 nm to 400 nm, from 40 nm to 350 nm, or from 50 nm to 300 nm).
  • the composite nanocarrier can comprise a plurality of composite nanocarriers that can be substantially monodisperse.
  • a monodisperse distribution of composite nanocarriers refers to composite nanocarrier the polydispersity index (PDI) as measured by dynamic light scattering is 0.35 or less (e.g., 0.30 or less, 0.25 or less, 0.20 or less, 0.15 or less, 0.10 or less, or 0.05 or less).
  • compositions described herein can be substantially stable. In some examples, the compositions can be substantially stable upon dilution.
  • substantially stable can refer to the stability of the average size of the composite nanocarriers over time and/or upon dilution.
  • the average size of the composite nanocarriers can change by 35% or less (e.g., 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less) over a period of time (e.g., 12 hours or more, 1 day or more, 1 week or more, 4 weeks or more, 8 weeks or more, or 12 weeks or more) and/or upon dilution.
  • the composition can comprise a plasmonic composition.
  • substantially stable can refer to the stability of the plasmonic properties of the composition.
  • the plasmonic composition can be stable over a period of time and/or upon dilution.
  • the composition can comprise a magnetic composition.
  • substantially stable can refer to the stability of the magnetic properties of the composition.
  • the magnetic composition can be stable over a period of time and/or upon dilution.
  • the nanoparticle comprises a fluorescent nanoparticle
  • the composition can comprise a fluorescent composition.
  • substantially stable can refer to the stability of the fluorescence of the composition.
  • the fluorescence of the composition can be stable upon dilution of the composition.
  • photoluminescence spectrum of the fluorescent composition can shift by 60 nm or less (e.g., 50 nm or less, 40 nm or less, 30 nm or less, 20 nm or less, or 10 nm or less) over a period of time (e.g., 1 hour or more, 12 hours or more, 1 day or more, 1 week or more, 4 weeks or more, 8 weeks or more, or 12 weeks or more) and/or upon dilution.
  • a period of time e.g., 1 hour or more, 12 hours or more, 1 day or more, 1 week or more, 4 weeks or more, 8 weeks or more, or 12 weeks or more
  • compositions can, in some examples, be biocompatible. In some examples, the compositions can be stable under physiological conditions.
  • compositions can comprise, in some examples, water and a cosolvent.
  • aqueous solutions can further comprise a cosolvent.
  • cosolvents include, but are not limited to, alcohols (e.g., methanol, ethanol, n-butanol, isopropanol, n-propanol), carboxylic acids (e.g., acetic acid), chloroform, and combinations thereof.
  • the aqueous solutions are substantially free of precipitate.
  • compositions disclosed herein are methods of making the compositions disclosed herein.
  • methods of making the compositions described herein the method comprising contacting the nanoparticle and the vesicle, thereby forming a mixture; and mixing the mixture, thereby at least partially encapsulating the nanoparticle within the vesicle (e.g., thereby forming the composite nanocarrier).
  • Mixing can be accomplished by mechanical stirring, shaking, vortexing, sonication (e.g., bath sonication, probe sonication), and the like.
  • the mixture is bath sonicated.
  • the mixture can be bath sonicated, for example, for 10 seconds or more (e.g., 20 seconds or more, 30 seconds or more, 40 seconds or more, 50 seconds or more, 1 minute or more, 2 minutes or more, 3 minutes or more, 4 minutes or more, 5 minutes or more, 6 minutes or more, 7 minutes or more, 8 minutes or more, 9 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 40 minutes or more, 50 minutes or more, 1 hour or more, 1.5 hours or more, 2 hours or more, 2.5 hours or more, 3 hours or more, 3.5 hours or more, 4 hours or more, or 4.5 hours or more).
  • the mixture can be bath sonicated for 5 hours or less (e.g., 4.5 hours or less, 4 hours or less, 3.5 hours or less, 3 hours or less, 2.5 hours or less, 2 hours or less, 1.5 hours or less, 1 hour or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less, 8 minutes or less, 7 minutes or less, 6 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1 minute or less, 50 seconds or less, 40 seconds or less, 30 seconds or less, or 20 seconds or less).
  • 5 hours or less e.g., 4.5 hours or less, 4 hours or less, 3.5 hours or less, 3 hours or less, 2.5 hours or less, 2 hours or less, 1.5 hours or less, 1 hour or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes
  • the amount of time for which the mixture is bath sonicated can range from any of the minimum values described above to any of the maximum values described above.
  • the mixture can be bath sonicated for from 10 seconds to 5 hours (e.g., from 10 seconds to 2.5 hours, from 2.5 hours to 5 hours, from 10 seconds to 1 hour, from 1 hour to 2 hours, from 2 hours to 3 hours, from 3 hours to 4 hours, from 4 hours to 5 hours, from 30 seconds to 40 minutes, from 1 minute to 30 minutes, or from 1 minute to 10 minutes).
  • the method can further comprise forming the vesicle.
  • the vesicle can, for example, be formed by self-assembly of the sterol and the surfactant.
  • forming the vesicle can comprise a one-step scalable method using CO2 expanded solvents called Depressurization of an Expanded Liquid Organic Solution-suspension (DELOS-susp) (Cano- Sarabia M et al. Langmuir 2008, 24, 2433-2437; Elizondo E et al. Nanomed. 2012, 7, 1391- 1408).
  • the method can further comprise forming the nanoparticle. Methods of making nanoparticles are known in the art.
  • the silicon nanocrystal can be synthesized according to previously reported methods (Hessel CM et al. Chem. Mater. 2012, 24, 393 ⁇ 401).
  • forming the silicon nanocrystal can include drying an organosilicone compound, such as silsesquioxane followed by heating the compound in a furnace.
  • the silicon containing compound can be heated up to 1200°C at a heating rate of 18°C/min. The temperature can be held for about an hour.
  • the reaction product can be etched with concentrated acid, such as hydrofluoric and hydrochloric acid, in the dark for about 4 to 6 hours.
  • the mixture can then purified by centrifugation for example at about 8000 rpm for 5 min then rinsed to yield the silicon containing nanoparticles.
  • compositions disclosed herein have potential applications in a number of fields such as imaging (e.g., biological imaging, fluorescence imaging, biomedical imaging), sensing (e.g., chemical sensing, biological sensing), medical applications (e.g., imaging, therapy, diagnostics, photothermal therapy, combinations thereof).
  • imaging e.g., biological imaging, fluorescence imaging, biomedical imaging
  • sensing e.g., chemical sensing, biological sensing
  • medical applications e.g., imaging, therapy, diagnostics, photothermal therapy, combinations thereof.
  • the compositions disclosed herein can be used in bioanalytical devices such as DNA chips, miniaturized biosensors and microfluidic devices.
  • the compositions can be used in gene expression profiling, drug discovery, and clinical diagnostics.
  • compositions can be used in applications benefiting from fluorescent labeling including medical and non-medical fluorescence microscopy, histology, flow cytometry, fundamental cellular and molecular biology protocols, fluorescence in situ hybridization, DNA sequencing, immuno assays, binding assays and separation.
  • compositions disclosed herein are methods of use of the composition disclosed herein, wherein the composition is used as a sensor to detect the presence or amount of a biological moiety; the structure, composition, and conformation of a biological moiety; the localization of a biological moiety in an environment; interactions of biological moieties; alterations in structures of biological compounds; alterations in biological processes; or combinations thereof.
  • the compositions can further comprise a targeting moiety that has an affinity for a biological target.
  • compositions disclosed herein are methods of use of the compositions disclosed herein in devices.
  • devices comprising the compositions disclosed herein.
  • devices include, but are not limited to, electronic devices, energy storage devices, energy conversion devices (e.g., solar cells, fuel cells, photovoltaic cells), optical devices (e.g., light emitting diodes), optoelectronic devices, bioanalytical devices, chemical sensors, biosensors, and combinations thereof.
  • the methods can comprise administering to the subject an amount of a composition as described herein; and detecting the composition.
  • the detecting can involve methods known in the art, for example, positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), X-ray, microscopy, computed tomography (CT).
  • PET positron emission tomography
  • SPECT single-photon emission computed tomography
  • MRI magnetic resonance imaging
  • X-ray X-ray
  • microscopy computed tomography
  • the composition can further comprise a detectable label, such as a radiolabel, fluorescent label, enzymatic label, and the like.
  • the detectable label can comprise the nanoparticle.
  • Such imaging methods can be used, for example, for assessing the extent of a disease and/or the target of a therapeutic agent.
  • the cells are indicative of a disease, such as cancer.
  • the disclosed compositions can be formulated in a physiologically- or pharmaceutically- acceptable form and administered by any suitable route known in the art including, for example, oral, nasal, rectal, topical, and parenteral routes of administration.
  • parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraperitoneal, and intrasternal administration, such as by injection.
  • Administration of the disclosed compositions can be a single administration, or at continuous or distinct intervals as can be readily determined by a person skilled in the art.
  • compositions disclosed herein can be formulated according to known methods for preparing pharmaceutically acceptable compositions. Formulations are described in detail in a number of sources which are well known and readily available to those skilled in the art. For example, Remington' s Pharmaceutical Science by E.W. Martin (1995) describes formulations that can be used in connection with the disclosed methods. In general, the compositions disclosed herein can be formulated such that an effective amount of the composition is combined with a suitable excipient in order to facilitate effective administration of the composition.
  • the compositions used can also be in a variety of forms. These include, for example, solid, semi- solid, and liquid dosage forms, such as tablets, pills, powders, liquid solutions or suspension, suppositories, injectable and infusible solutions, and sprays.
  • compositions also preferably include conventional pharmaceutically-acceptable carriers and diluents which are known to those skilled in the art.
  • carriers or diluents for use with the compositions include ethanol, dimethyl sulfoxide, glycerol, alumina, starch, saline, and equivalent carriers and diluents.
  • the compositions disclosed herein can advantageously comprise between 0.1% and 100% by weight of the total of one or more of the subject composite nanocarriers based on the weight of the total composition including carrier or diluent.
  • Formulations suitable for administration include, for example, aqueous sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient; and aqueous sterile suspensions, which can include suspending agents and thickening agents.
  • the formulations can be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and can be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use.
  • Extemporaneous injection solutions and suspensions can be prepared from sterile powder, granules, tablets, etc. It should be understood that in addition to the excipients particularly mentioned above, the compositions disclosed herein can include other agents conventional in the art having regard to the type of formulation in question.
  • compositions disclosed herein can be administered to a patient in need of treatment in combination with other substances and/or treatments. These other substances or treatments can be given at the same as or at different times from the compositions disclosed herein.
  • compositions disclosed herein can be locally administered at one or more anatomical sites, such as sites of unwanted cell growth (such as a tumor site or benign skin growth, e.g., injected or topically applied to the tumor or skin growth), optionally in combination with a pharmaceutically acceptable carrier such as an inert diluent.
  • a pharmaceutically acceptable carrier such as an inert diluent
  • the compositions disclosed herein can be systemically administered, such as intravenously or orally, optionally in combination with a pharmaceutically acceptable carrier such as an inert diluent, or an assimilable edible carrier for oral delivery. They can be enclosed in hard or soft shell gelatin capsules, can be compressed into tablets, or can be incorporated directly with the food of the patient' s diet.
  • compositions can be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, aerosol sprays, and the like.
  • the tablets, troches, pills, capsules, and the like can also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; diluents such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring can be added.
  • binders such as gum tragacanth, acacia, corn starch or gelatin
  • diluents such as dicalcium phosphate
  • a disintegrating agent such as corn starch, potato starch, alginic acid and the like
  • a lubricant such as magnesium stearate
  • a sweetening agent such as sucrose, fructose, lactose or aspart
  • the unit dosage form When the unit dosage form is a capsule, it can contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials can be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules can be coated with gelatin, wax, shellac, or sugar and the like.
  • a syrup or elixir can contain the composition, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor.
  • any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed.
  • the compositions can be incorporated into sustained-release preparations and devices.
  • compositions disclosed herein can be administered intravenously, intramuscularly, or intraperitoneally by infusion or injection.
  • Solutions of the compositions can be prepared in water, optionally mixed with a nontoxic surfactant.
  • Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations can contain a preservative to prevent the growth of microorganisms.
  • the pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient, which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions.
  • the ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage.
  • the liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof.
  • the proper fluidity can be maintained, for example, by the
  • the prevention of the action of microorganisms can be brought about by various other antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.
  • various other antibacterial and antifungal agents for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.
  • isotonic agents for example, sugars, buffers or sodium chloride.
  • compositions can be brought about by the inclusion of agents that delay absorption, for example, aluminum monostearate and gelatin.
  • Sterile injectable solutions are prepared by incorporating the compositions disclosed herein in the required amount in the appropriate solvent with various other ingredients enumerated above, as required, followed by filter sterilization.
  • the preferred methods of preparation are vacuum drying and the freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions.
  • Useful liquid carriers include water, alcohols or glycols or water-alcohol/glycol blends, in which the compositions can be dispersed at effective levels, optionally with the aid of nontoxic surfactants.
  • Adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use.
  • the resultant liquid compositions can be applied from absorbent pads, used to impregnate bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprayers, for example.
  • Thickeners such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like, for application directly to the skin of the subject.
  • compositions that comprise the compositions disclosed herein in combination with a pharmaceutically acceptable excipient.
  • kits that comprise a composition disclosed herein in one or more containers.
  • the disclosed kits can optionally include pharmaceutically acceptable carriers and/or diluents.
  • a kit includes one or more other components, adjuncts, or adjuvants as described herein.
  • a kit includes one or more anti-cancer agents, such as those agents described herein.
  • a kit includes instructions or packaging materials that describe how to administer a composition of the kit.
  • Containers of the kit can be of any suitable material, e.g. , glass, plastic, metal, etc., and of any suitable size, shape, or configuration.
  • a composition disclosed herein is provided in the kit as a solid, such as a tablet, pill, or powder form.
  • a composition disclosed herein is provided in the kit as a liquid or solution.
  • the kit comprises an ampoule or syringe containing a composition disclosed herein in liquid or solution form.
  • Nanoparticles have been studied for biomedical imaging applications due to their fluorescence properties and photostability, though many systems utilize heavy metals such as cadmium (Michalet X et al. Science 2005, 307, 538-544; Kovalenko MV et al. ACS Nano 2015, 9, 1012-1057).
  • Silicon nanocrystals offer a biocompatible alternative to toxic quantum dots that exhibit emission in the visible to near-infrared region (NIR) (Hessel CM et al. Chem. Mater. 2012, 24, 393-401; Park JH et al. Nat. Mater. 2009, 8, 331-336; Henderson EJ et al.
  • silicon nanocrystals can be stably dispersed in organic solvents following the covalent attachment of capping ligands, but such silicon nanocrystals have not been stably dispersed in water (Hessel CM et al. Chem. Mater. 2012, 24, 393-401 ; Henderson EJ et al. Small 2011, 7, 2507-2516; O'Farrell N et al. Int. J. Nanomedicine 2006, 1, 451-472; Yu Y et al. Langmuir 2013, 29, 1533- 1540; Erogbogbo F et al. ACS Nano 2008, 2, 873-878). Silicon nanocrystals for use in medical applications should be dispersible in water.
  • Non- liposomal nanovesicular structures can be formed for example using equimolar amounts of sterols, such as cholesterol (chol), and quaternary ammonium surfactants, such as CTAB (Ferrer-Tasies L et al. Langmuir 2013, 29, 6519-6528).
  • sterols such as cholesterol (chol)
  • CTAB quaternary ammonium surfactants
  • vesicular structures exhibit a high vesicle to vesicle homogeneity regarding size, lamellarity, and membrane supramolecular organization, which are all properties that can impact the use of such formulations in medical or diagnosis applications (Elizondo E et al. /. Am. Chem. Soc. 2012, 134, 1918-1921; Cabrera I et al. Nano Lett. 2013, 13, 3766-3774). Contrary to micellar structures formed exclusively with quaternary ammonium surfactants, the morphology of these vesicular nanostructures is substantially unaffected upon increasing the temperature or by dilution, making them attractive candidates for use in-vivo.
  • the nanovesicles can be prepared by a one-step scalable method using CO2 expanded solvents called Depressurization of an Expanded Liquid Organic Solution-suspension (DELOS-susp) (Cano-Sarabia M et al. Langmuir 2008, 24, 2433-2437; Elizondo E et al.
  • DELOS-susp Expanded Liquid Organic Solution-suspension
  • nanovesicles are stable aqueous colloidal structures and they have antibacterial and anti-biofilm properties. These results make them promising nanocarriers in the development of new nanovesicle-nanocrystal hybrids.
  • Silicon nanocrystals were synthesized according to previously reported methods (Hessel CM et al. Chem. Mater. 2012, 24, 393-401). Briefly, hydrogen silsesquioxane (HSQ, Dow Corning) was degassed and then heated at 1100°C for 60 minutes in a tube furnace under forming gas flow. The resulting brown material was then ground with a mortar and pestle, followed by further size reduction by mechanical shaking in a wrist action shaker with borosilicate beads for 9 hours. The final brown powder comprised crystalline silicon embedded in a S1O2 matrix.
  • HSQ hydrogen silsesquioxane
  • SiNC silicon nanocrystal
  • HCl hydrochloric acid
  • HF hydrofluoric acid
  • the material was precipitated by centrifugation for 5 minutes at 8000 rpm.
  • the HF was removed and the precipitate was redispersed in ethanol (Pharmco-Aaper), and then centrifuged again. This washing process was repeat once more with ethanol and then once with chloroform (>99.8%, Fisher), resulting in -H terminated silicon nanocrystals.
  • the 1-octene solution was removed on a rotary evaporated at 760 mmHg and 60°C, after which the silicon nanocrystals were redispersed in hexanes (>98.5%, Fisher).
  • the silicon nanocrystals were then washed using ethanol as an antisolvent and hexanes as the solvent 4 times through centrifugation.
  • the final silicon nanocrystals were dispersed in chloroform, and imaged using transmission electron microscopy (TEM) ( Figure 1 - Figure 3).
  • TEM transmission electron microscopy
  • Thermogravimetric analysis was conducted on silicon nanocrystals to determine the mass per nanocrystal of silicon vs. ligand ( Figure 5).
  • Thermal gravimetric analysis data were acquired on a Mettler Toledo TGA/DSC 1. Silicon nanocrystals dispersed in chloroform were drop cast and dried into a 70 ⁇ alumina crucible (Mettler Toledo). The sample was then heat under 50 ml per minute air flow at a rate of 10°C per minute from 25°C to 800°C and then held at 800°C for 30 minutes. It was assumed that at the beginning of the thermogravimetric analysis cycle the sample comprised a silicon core and octene ligands, while at the end of the cycle there was no remaining ligands and all the silicon had been converted to S1O2. From the following the thermogravimetric analysis cycle.
  • thermogravimetric analysis data and the known size of silicon nanocrystal core (2.8 + 0.6 nm), it was determined that the total mass per silicon nanocrystal is 7.24 x 10 "17 mg, of which approximately 37% is the silicon core and 63% is ligand (corresponding to a ligand coverage of 9.93 ligands/nm 2 ).
  • Nanovesicles were synthesized using the DELOS-susp procedure, with cholesterol (chol, Anatrace) as the sterol and cetyl trimethylammonium bromide (CTAB, high purity grade, Amresco) as the quaternary ammonium surfactant (Cano-Sarabia M et al. Langmuir 2008, 24, 2433-2437; Cabrera I et al. Nano Lett. 2013, 13, 3766-3774). Briefly, a 7.5 ml high-pressure vessel was loaded with a solution containing 76 mg of cholesterol in 2.88 ml of ethanol at atmospheric pressure and 35°C.
  • the molar ratio between the CTAB and the cholesterol in the final formulation was 1 to 1, which has been shown to be the correct proportion in order to have a pure vesicular phase (Ferrer-Tasies L et al. Langmuir 2013, 29, 6519-6528).
  • the final concentration of nanovesicles in this vesicular phase 7 mM cholesterol-CTAB nanovesicles, included 7 mM cholesterol and 7 mM CTAB in high purity water containing 10% ethanol.
  • Nanovesicles with a final concentration of 0.7 mM CTAB and 0.7 mM in cholesterol where prepared by dilution of the 7 mM cholesterol-CTAB nanovesicles with water containing 10% ethanol.
  • Silicon nanocrystals with core diameters of approximately 2.8 nm and 1-octene capping ligands were incorporated into pre-formed cholesterol-CTAB nanovesicles using a 5 minute bath sonication procedure, as outlined in Figure 6. Unless otherwise noted, the following proportions were used: 750 ⁇ of 7 mM cholesterol-CTAB nanovesicles were added to a 2 ml glass vial. 20 ⁇ of 6.75 mg/ml silicon nanocrystals (0.135 mg) was added.
  • the vial with the 750 ⁇ of 7 mM cholesterol-CTAB nanovesicles and 20 ⁇ of 6.75 mg/ml silicon nanocrystals (0.135 mg) was then bath sonicated for 5 minutes to incorporate the silicon nanocrystals (Misonix 1510R-MT or Bransonic Ml 800 bath sonicator, 40 kHz, 1/2 gallon tank). All experiments were conducted under room temperature conditions.
  • Cryogenic transmission electron microscopy (cryo-TEM) images were taken using an FEI Tecnai Biotwin TEM operated at 80 kV accelerating voltage, and acquired digitally.
  • Cryo- TEM samples were prepared using a Leica EM GP by dropping 3 ⁇ of sample onto Quantifoil Rl.2/1.3 holey carbon on 300 mesh copper grids (Electron Microscopy Science) inside the environmental control chamber set to 25 °C and 90% humidity. After a blotting time of 3.5 seconds, the grid was plunged into liquid ethane to vitrify the sample. The grid was then transferred to a Gatan 626 Cryo-Transfer Holder under liquid nitrogen. FEI low dose software was used to obtain images of cryo-TEM samples.
  • Figure 10- Figure 15 show cryo-TEM images of the silicon nanocrystals incorporated into nanovesicles. Although many of the nanovesicles are free of silicon nanocrystals, there was still a significant amount of association between the silicon nanocrystals and the nanovesicles. The silicon nanocrystals formed aggregates that were either on one side of one or multiple nanovesicles or that appeared to form spherical structures with similar sizes as the nanovesicles without silicon nanoparticles.
  • Nanovesicles are composed of two component building blocks, cholesterol and CTAB, such that geometric calculations could be used to estimate the number of each molecule in a spherical nanovesicle.
  • the radius of an average surface of both membranes (Rs) was used to estimate the number of cholesterol-CTAB pairs in a typical nanovesicle ( Figure 16). This radius is given by:
  • d is the vesicle diameter and could be estimated from dynamic light scattering (DLS) data of nanovesicles (assuming spherical geometry and unimodal size distribution) that had been bath sonicated with 20 ⁇ of chloroform (no silicon nanocrystals) as seen in Figure 7, which was found to be 113.7 + 0.4 nm.
  • N s the number of cholesterol- CTAB pairs
  • a is the area of the polar head group of a cholesterol-CTAB pair, and can be estimated from just the headgroup of the CTAB surfactant, 0.64 nm 2 ( Figure 17) (Ferrer-Tasies L et al. Langmuir 2013, 29, 6519-6528). Using all these parameters the estimated number of bimolecular building-block cholesterol-CTAB (Ns) in a single layer typical nanovesicle is 58,643, and thus in a bilayer nanovesicle there are approximately 117,286 cholesterol-CTAB pairs.
  • Figure 18 shows the absorbance (Varian Cary 50 Bio ultra violet- visible
  • spectrophotometer or Varian Cary 500 ultraviolet-visible-near infrared spectrophotometer), photoluminescence excitation (PL) and photoluminescence emission (PLE) spectra (Varian Cary Eclipse fluorescence spectrophotometer) collected from silicon nanoparticles dispersed in chloroform and incorporated into nanovesicles. Spectra were measured at room temperature by diluting nanovesicle-silicon nanocrystal dispersions by a factor of 20 with water in glass cuvettes, and the average photoluminescence emission wavelength was calculated from the photoluminescence curve. The spectra of each sample are similar ( Figure 18), indicating that the incorporation of the nanocrystals into the nanovesicles, in an aqueous media, did not change the fluorescence properties of the nanocrystals.
  • Samples of silicon nanocrystals dispersed with cholesterol-CTAB nanovesicles in water with 10% ethanol were prepared through 5 minutes of bath sonication and monitored for 12 weeks, along with control samples prepared with only CTAB, no nanovesicles, or no silicon nanocrystals, as outlined in Table 1 and Figure 19- Figure 23).
  • Table 1 Description of samples i-v monitored in stability testing.
  • the nanovesicles were diluted in 10% EtOH in water to 0.7 mM cholesterol-CTAB (chol-CTAB) nanovesicles, which is below the CTAB critical micelle concentration of 1 mM, and 750 ⁇ of nanovesicles with 20 ⁇ silicon
  • nanocrystals in chloroform were bath sonicated to form sample ii.
  • Cryo-TEM images ( Figure 26- Figure 29) of sample ii indicate that the structures formed are similar to those when 7 mM cholesterol-CTAB nanovesicles was used (sample i), including one sided and full nanovesicle aggregates. Silicon nanocrystals appear to incorporate into nanovesicles similarly to when nanovesicles were at concentrations about the CTAB CMC of 1 mM ( Figure 30- Figure 41). The fact that the nanovesicles both above and below the 1 mM CTAB CMC have similar stability suggests that the nanovesicles have a high ability to stabilize nanocrystals even when working with diluted systems.
  • Silicon nanocrystals could also be dispersed with 7 mM CTAB micelles (with no cholesterol) with good dispersion and fluorescence stability, though the shape of the nanocrystal aggregates were quite different than those stabilized by the nanovesicles.
  • Figure 42- Figure 45 shows cryo-TEM images of CTAB -stabilized nanocrystals with irregularly shaped aggregates that were both very small and very large. For medical applications consistent size and concentration of load delivery is important, and thus the wide size distribution observed with CTAB micelles would not be ideal for those applications.
  • FIG. 30- Figure 41 shows images of sample (i) over a period of 12 weeks. There were no observed changes in size or shape during this time period. Over all time points, silicon nanocrystals were observed aggregated into one side of some nanovesicles and forming spherical structures with the same size as plain nanovesicles. Dynamic light scattering data were also acquired to monitor the size distribution in the mixtures over time.
  • Dynamic light scattering (DLS) data were acquired on a Zetasizer Nano ZS (Malvern Instruments). Samples were measured in 40 ⁇ disposable cuvettes at 173°, with temperature set to 25 °C. All measurements were conducted in triplicate. Zetasizer software (Malvern
  • nanovesicles were prepared with no ethanol using a sonication methodology previously described (Ferrer-Tasies L et al. Langmuir 2013, 29, 6519-6528). Briefly: 39 mg of cholesterol and 36 mg of CTAB were weighed into a glass bottle and suspended in 10 ml of deionized water. The dispersion was then sonicated at room temperature (25 °C) for 4 minutes (Sonic and Materials Corporation, 20 kHz) to form a homogeneous dispersion.
  • silicon nanocrystals were incorporated using the standard incorporation process (20 ⁇ silicon nanocrystals in chloroform added to 750 ⁇ nanovesicles, then bath sonicated for 5 minutes).
  • DOPC 35 mg, in chloroform, Avanti Polar Lipids
  • DOPC 35 mg, in chloroform, Avanti Polar Lipids
  • the system was kept at 35 °C and 10 MPa for approximately 1 hour to achieve homogenization and to attain thermal equilibration.
  • the C02-expanded DOPC solution was depressurized over 9 ml of an aqueous solution to create the liposomes.
  • the final concentration of DOPC in the liposomal system was 3.6 mM in high purity water containing 17% ethanol.
  • DOPG liposomes were formed by drying 7 ⁇ DOPG (in chloroform, Avanti Polar Lipids) from chloroform into a film with a rotary evaporator for 15 minutes. Residual solvent was removed by placing the film in a vacuum oven for 2 hours. The film was then hydrated with 1 ml of 10 mM HEPES, 10 mM NaCl and bath sonicated for 30 minutes. Finally, the suspension was extruded 21 times through a 100 nm pore size polycarbonate filter on an Avanti MiniExtruder (Avanti Polar Lipids).
  • the bath sonication approach to silicon nanocrystal incorporation was also carried out for the preparation of the silicon nanocrystal-liposomes dispersions. Briefly, 20 ⁇ of 6.75 mg/ml silicon nanocrystals (0.135 mg) was added to 750 ⁇ of either 3.6 mM DOPC or 7 mM DOPG liposomes and then bath sonicated for 5 minutes.
  • the vial containing the DOPC and silicon nanocrystals also had a white precipitate at the bottom vial that was likely large lipid structures.
  • the anionic DOPG liposomes retained their initial size, but no silicon nanocrystals were observed to associate with the liposomes, as shown in Figure 61- Figure 64.
  • the dispersion was fluorescent and separate lipid-stabilized aggregates of silicon nanocrystals were observed. These dispersions lost their fluorescence after the third day.
  • nanovesicles 7 mM cholesterol-CTAB
  • 135 ⁇ g of silicon nanocrystals was added to each vial, though at different concentrations and thus in different volumes of chloroform.
  • the amounts added were: (i) 10 ⁇ of 13.5 mg/ml silicon nanocrystal in chloroform, (ii) 20 ⁇ of 6.75 mg/ml silicon nanocrystal in chloroform (typical conditions), (iii) 40 ⁇ of 3.375 mg/ml silicon nanocrystal in chloroform, (iv) 80 ⁇ of 1.6875 mg/ml silicon nanocrystal in chloroform, (v) 200 ⁇ of 0.675 mg/ml silicon nanocrystal in chloroform.
  • the white precipitate suggests that the chloroform destabilized the cholesterol-CTAB nanovesicle structures and caused them to break from their typically sized dispersions This suggests that the high volume fraction of chloroform added with the silicon nanocrystals had a destabilizing effect on the nanovesicles and caused the structures to break apart.
  • the experiments to determine how the chloroform may interact with the nanovesicles found that the volume ratio of nanovesicles to silicon nanocrystals in chloroform influenced the stability of the assemblies.
  • a small amount of chloroform can enhance the incorporation of dodecanethiol-capped gold nanocrystals into liposomes (Rasch MR et al. Langmuir 2012, 28, 12971-12981) and a similar interaction may be occurring with nanovesicles, resulting in successful incorporation without destroying the nanovesicles when 20 ⁇ of chloroform is added. This is further confirmed by sample (v) in Figure 19- Figure 23, where 20 ⁇ of chloroform without silicon nanocrystals was added to nanovesicles and bath sonication was performed with no resulting precipitation of material, suggesting that that amount of chloroform could not destabilize the nanovesicle structure.
  • probe sonication and vortexing were both used to provide energy to the system, however neither approach was successful.
  • a probe sonicator (Branson Sonifier 250, Output control: 2, constant duty cycle) was used for 3 minutes with the cholesterol-CTAB nanovesicles and silicon nanocrystals, and within one day aggregates were observed (Figure 80).
  • the probe sonicated sample lost fluorescence over a period of a month and a half following probe sonication, likely indicating that the nanoparticles had degraded.
  • the silicon nanocrystals have a hydrophobic coating, so they tend to aggregate when dispersed in water due to the strong attractive hydrophobic interaction. As the aggregates or clusters of particles form, they interact with other clusters of particles and with the hydrophilic surfaces of nanovesicles.
  • the capping layer is compact and the interaction of a nanovesicle with a cluster of silicon particles is reminiscent of the interaction of a vesicle with a hydrophobic solid surface.
  • the layers of the nanovesicles were spread onto the surface of the clusters of silicon particles. This spreading process requires first the breaking of vesicles and the input of energy.
  • Vesicles are dynamic structures that can be reformed or reduced in size with the addition of sonication energy (Marsh D. Handbook of Lipid Bilayers, Second Edition; CRC Press, 2013; Szoka F and Papahadjopoulos D. Annu. Rev. Biophys. Bioeng. 1980, 9, 467-508).
  • sonication energy Marsh D. Handbook of Lipid Bilayers, Second Edition; CRC Press, 2013; Szoka F and Papahadjopoulos D. Annu. Rev. Biophys. Bioeng. 1980, 9, 467-508.
  • cholesterol-CTAB nanovesicles with silicon nanocrystals were sonicated for 15 or 30 min, they were smaller than those sonicated for 1 minute or 5 minutes (Figure 52- Figure 56).
  • nanovesicles are sonicated they are broken down through a redistribution of membrane molecules.
  • this redistribution would allow small aggregates of silicon nanocrystals to become stabilized by the hydrophobic part of cholesterol-CTAB monolayers ( Figure 86).
  • the resulting self-assembled structure (clusters of silicon particles covered by a nanovesicle monolayer) is now stable in water and acquires the radius
  • cryo-TEM images of silicon nanocrystals incorporated into cholesterol-CTAB nanovesicles in Figure 10- Figure 15 show that the silicon nanocrystal aggregations are approximately the same size as the nanovesicles without any silicon nanocrystals. Since the size of the nanovesicles is influenced by the interaction between cholesterol and CTAB, the size of silicon nanocrystals aggregated suggests that they are associated with the same cholesterol-CTAB units. Further, as shown in the dilution experiment in Figure 65 - Figure 73, only silicon nanocrystal dispersed in nanovesicles remain stable after several rounds of dilution, while silicon nanocrystal dispersed in CTAB micelles result in precipitation of the silicon nanocrystals after multiple dilutions. Thus, it is specifically the nanovesicles where cholesterol and CTAB interact as bimolecular building blocks that contribute to stabilizing the silicon nanocrystals.
  • a method to disperse fluorescent silicon nanocrystals in aqueous media with long-term stability was developed, utilizing cholesterol-CTAB nanovesicles, which are non-liposomal vesicular structures.
  • the stable silicon nanocrystal-nanovesicle aqueous dispersions can be made with five minutes of bath sonication.
  • the silicon nanocrystal-nanovesicle assemblies remain dispersed in water for several weeks and maintain the fluorescence properties of the silicon nanocrystals for several weeks ( Figure 87).
  • the silicon nanocrystal-nanovesicle assemblies also maintain the fluorescence properties of the silicon nanocrystals after dilution with additional water.
  • Cryogenic transmission electron microscopy (cryo-TEM) imaging further confirmed that these assemblies retained their structure for several weeks.
  • Conditions for incorporating the nanocrystals into nanovesicles were investigated, including the use of a bath sonication incorporation process.
  • Nanovesicles which have been shown to have long term stability (e.g., at least three years in aqueous solutions) (Ferrer-Tasies L et al. Langmuir 2013, 29, 6519-6528), provide a vehicle for the dispersion of hydrophobic silicon nanocrystals into in vitro or in vivo environments, even under dilute conditions.
  • the biocompatibility of nanovesicles and near infrared emitting silicon nanocrystals make these structures excellent candidates for biomedical imaging applications.
  • nanovesicles have been shown to enhance protein activity and to protect proteins against premature degradation in topical pharmaceutical formulations, as well as to treat biofilms (Thomas N et al. /. Mater. Chem. B 2015, 3, 2770-2777; WO 2014/019555). Therefore, the incorporation of both biomolecules and silicon nanocrystals into nanovesicle structures offers the possibility to explore the behavior of these systems in biological environments and their use for theranostics.

Abstract

La présente invention concerne des compositions contenant une solution aqueuse comprenant un nanosupport composite, le nanosupport composite comprenant une nanoparticule au moins partiellement encapsulée dans une vésicule, la vésicule comprenant un stérol et un tensioactif. Dans certains exemples, la vésicule est constituée d'un stérol et d'un tensioactif. Dans certains exemples, le stérol comprend du cholestérol ou un dérivé de celui-ci. Dans certains exemples, le tensioactif comprend un tensioactif à base d'ammonium quaternaire, tel que le bromure de cétyltriméthylammonium. Dans certains exemples, la nanoparticule comprend du Si. Les compositions de l'invention peuvent être essentiellement stables. L'invention concerne également des procédés de préparation et des procédés d'utilisation de la composition de l'invention.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020229469A1 (fr) 2019-05-13 2020-11-19 Fundació Hospital Universitari Vall D'hebron - Institut De Recerca Nanovésicules et leur utilisation pour l'administration d'acides nucléiques
WO2024028283A1 (fr) * 2022-08-03 2024-02-08 Nanomol Technologies, S.L. Vésicules à base de tensioactifs dérivés du glucose et de phytostérols

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001061045A1 (fr) * 2000-02-18 2001-08-23 Biocrystal Ltd. Nanocristaux fluorescents encapsules fonctionnalises
WO2002029410A2 (fr) * 2000-10-06 2002-04-11 Quantum Dot Corporation Cellules dotees d'une signature spectrale et procedes de preparation et utilisation desdites cellules
WO2012094727A1 (fr) * 2010-10-29 2012-07-19 The Governing Council Of The University Of Toronto Encapsulation par lipides de nanoparticules pour diffusion raman exaltée de surface (sers)
WO2014019555A1 (fr) 2012-08-02 2014-02-06 Centro De Ingenieria Genetica Y Biotecnologia Vésicules comprenant le facteur de croissance épidermique et compositions les contenant
WO2014089698A1 (fr) * 2012-12-11 2014-06-19 Zamecnik Colin R Nanoparticules de métal noble enrobées de colorant et encapsulées dotées de propriétés améliorées de diffusion raman exaltée de surface, utilisées comme agents de contraste
US8859727B2 (en) * 2005-03-14 2014-10-14 The Board Of Regents Of The University Of Texas System Bioactive FUS1 peptides and nanoparticle-polypeptide complexes

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001061045A1 (fr) * 2000-02-18 2001-08-23 Biocrystal Ltd. Nanocristaux fluorescents encapsules fonctionnalises
WO2002029410A2 (fr) * 2000-10-06 2002-04-11 Quantum Dot Corporation Cellules dotees d'une signature spectrale et procedes de preparation et utilisation desdites cellules
US8859727B2 (en) * 2005-03-14 2014-10-14 The Board Of Regents Of The University Of Texas System Bioactive FUS1 peptides and nanoparticle-polypeptide complexes
WO2012094727A1 (fr) * 2010-10-29 2012-07-19 The Governing Council Of The University Of Toronto Encapsulation par lipides de nanoparticules pour diffusion raman exaltée de surface (sers)
WO2014019555A1 (fr) 2012-08-02 2014-02-06 Centro De Ingenieria Genetica Y Biotecnologia Vésicules comprenant le facteur de croissance épidermique et compositions les contenant
WO2014089698A1 (fr) * 2012-12-11 2014-06-19 Zamecnik Colin R Nanoparticules de métal noble enrobées de colorant et encapsulées dotées de propriétés améliorées de diffusion raman exaltée de surface, utilisées comme agents de contraste

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
ALENAIZI R ET AL., PHYSICOCHEM. ENG. ASPECTS, vol. 482, 2015, pages 662 - 669
ANTONIETTI M; FORSTER S., ADV. MATER., vol. 15, 2003, pages 1323 - 1333
CABRERA I ET AL., NANO LETT., vol. 13, 2013, pages 3766 - 3774
CANHAM LT, APPL. PHYS. LETT., vol. 57, 1990, pages 1046 - 1048
CANO-SARABIA M ET AL., LANGMUIR, vol. 24, 2008, pages 2433 - 2437
CULLIS AG ET AL., J. APPL. PHYS., vol. 82, 1997, pages 909 - 965
E.W. MARTIN, REMINGTON'S PHARMACEUTICAL SCIENCE, 1995
ELIZONDO E ET AL., J. AM. CHEM. SOC., vol. 134, 2012, pages 1918 - 1921
ELIZONDO E ET AL., NANOMED, vol. 7, 2012, pages 1391 - 1408
ELIZONDO E ET AL., NANOMED., vol. 7, 2012, pages 1391 - 1408
EROGBOGBO F ET AL., ACS NANO, vol. 2, 2008, pages 873 - 878
FERRER-TASIES L ET AL., LANGMUIR, vol. 29, 2013, pages 6519 - 6528
HENDERSON EJ ET AL., SMALL, vol. 7, 2011, pages 2507 - 2516
HESSEL CM ET AL., CHEM. MATER., vol. 24, 2012, pages 393 - 401
KOVALENKO MV ET AL., ACS NANO, vol. 9, 2015, pages 1012 - 1057
MARSH D.: "Handbook of Lipid Bilayers", 2013, CRC PRESS
MICHALET X ET AL., SCIENCE, vol. 307, 2005, pages 538 - 544
O'FARRELL N ET AL., INT. J. NANOMEDICINE, vol. 1, 2006, pages 451 - 472
O'FARRELL N ET AL., INT. J. NANOMEDICINE, vol. 7, 2006, pages 451 - 472
PARK JH ET AL., NAT. MATER., vol. 8, 2009, pages 331 - 336
RASCH MR ET AL., LANGMUIR, vol. 28, 2012, pages 12971 - 12981
SZOKA F; PAPAHADJOPOULOS D., ANNU. REV. BIOPHYS. BIOENG., vol. 9, 1980, pages 467 - 508
THOMAS N ET AL., J. MATER. CHEM. B, vol. 3, 2015, pages 2770 - 2777
YU Y ET AL., LANGMUIR, vol. 29, 2013, pages 1533 - 1540

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020229469A1 (fr) 2019-05-13 2020-11-19 Fundació Hospital Universitari Vall D'hebron - Institut De Recerca Nanovésicules et leur utilisation pour l'administration d'acides nucléiques
WO2024028283A1 (fr) * 2022-08-03 2024-02-08 Nanomol Technologies, S.L. Vésicules à base de tensioactifs dérivés du glucose et de phytostérols

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