GB2440910A - A marker for studying drug dynamics in vivo - Google Patents
A marker for studying drug dynamics in vivo Download PDFInfo
- Publication number
- GB2440910A GB2440910A GB0616415A GB0616415A GB2440910A GB 2440910 A GB2440910 A GB 2440910A GB 0616415 A GB0616415 A GB 0616415A GB 0616415 A GB0616415 A GB 0616415A GB 2440910 A GB2440910 A GB 2440910A
- Authority
- GB
- United Kingdom
- Prior art keywords
- microbiodot
- previous
- dye
- polymer
- marker
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 22
- 239000003550 marker Substances 0.000 title abstract 5
- 238000001727 in vivo Methods 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 21
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 9
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 9
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 4
- 238000002347 injection Methods 0.000 claims abstract description 4
- 239000007924 injection Substances 0.000 claims abstract description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract 4
- 229910052742 iron Inorganic materials 0.000 claims abstract 2
- 239000000975 dye Substances 0.000 claims description 16
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 230000004069 differentiation Effects 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 239000011573 trace mineral Substances 0.000 claims description 2
- 235000013619 trace mineral Nutrition 0.000 claims description 2
- 210000003462 vein Anatomy 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims 2
- 239000002105 nanoparticle Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 abstract description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 abstract description 2
- 229920000954 Polyglycolide Polymers 0.000 abstract description 2
- 229920002988 biodegradable polymer Polymers 0.000 abstract description 2
- 239000004621 biodegradable polymer Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 229920000747 poly(lactic acid) Polymers 0.000 abstract description 2
- 238000007885 magnetic separation Methods 0.000 abstract 1
- 239000002077 nanosphere Substances 0.000 abstract 1
- 239000004626 polylactic acid Substances 0.000 abstract 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- -1 poly(alkylene glycol Chemical compound 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920001273 Polyhydroxy acid Polymers 0.000 description 1
- 229920002651 Polysorbate 85 Polymers 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000001046 green dye Substances 0.000 description 1
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 1
- 229960004657 indocyanine green Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001896 polybutyrate Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940113171 polysorbate 85 Drugs 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
- A61K49/0034—Indocyanine green, i.e. ICG, cardiogreen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
- A61K49/0043—Fluorescein, used in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Nanotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The marker 1 comprises an outer biodegradable, non toxic polymer shell 1, prepared from a biodegradable polymer such as copolymer of polylactic acid and polyglycolide. Inside the shell is a non-toxic fluorescent dye composition. The polymer coat is transparent in parts such that the fluorescence emission can be detected from an intact marker. The shell may contain nanospheres of soft iron 6, to facilitate magnetic separation. The marker is intended to be mixed with a drug for administration by injection or oral routes and is intended to have a lifetime similar to that of the drug. The degree of biodegradability may be modified to influence the lifetime of the marker in the body.
Description
<p>The Microbjodot This invention relates to identification of ingested or
injected drugs using tagging in the form of a microdot that is included with the drug or drugs.</p>
<p>When drugs, either prescription or over the counter, are taken into the body by injection or orally they can be very costly in terms of finance or time consuming methods of finding out in what concentration or what they are in the body.</p>
<p>To overcome this, use of a microdot is intimately mixed with the drug and instead of the drug being analysed the microdot itself is identified.</p>
<p>The drug is either injected intravenously or taken orally.If injected, the dot passes with the drug directly to the bloodstream and can be viewed microscopically.If it is orally taken the dot must be small enough to enter the villi of the small intestine and enter the blood by this route, hence the dot must be about a few nanometres upto 500 microns in diameter for bloodstream entrance.</p>
<p>The dots must have a lifetime in the body equal to that of the drug it is mixed but after expiration of this lifetime they must be fully biodegraded by the body so as other drugs taken after are not confused in with the others after first drugs' effect has ceased.The lifetime of the dots may therefore vary from a few hours upto months depending on drugs' effects.</p>
<p>The dot is composed of an inner filling of a fluorescent,non-toxic dye and a outer semi-transparent in parts, coat of a biodegradable,non-toxic polymer.The type of dye used varies, as does the polymer and thickness of polymer used.</p>
<p>Identification of the dot is done by illuminating a sample of the patient's blood using a special light source whose wavelength and luminosity can be carefully recorded and controlled.The dots that, occur in the blood, fluoresce under the light when a special wavelength is used and their spectrorscopic waves can be analysed to find Out which dot they are and hence what drug they are mixed with.The outer polymer coat is transparent in parts so as to allow in the waves from the light source to cause fluorescence of the dye underneath and the parts of the cdát that have been doped are therefore modifying the exiting fluorescent waves. This coat may be varied in opacity to light passing out and also it may be varied in colour and density to make different dots for different drugs.Also, of course, the central dye may be varied.</p>
<p>An example of a dot is maybe polymer wall thickness between 100 nanometres to 660 nanometres and the overall dot diameter is say between 0.5 and 8 microns for intravascular injection and a diameter of between 0.5 and 5 millimetres for oral administration.</p>
<p>Substances that may be used as polymer coats are suggested as:-Poly(ethylene-co-acrylic acid),PBAT which is poly(butyIadiptateco terepthalate),P.L.A. which is Polylactide mixed with plastizers if necessary also polylactic acid-co-glycolic acid and polyhydroxy acid as a polyglycolide.The polymers mentioned are non-toxic,biodegradable and may be transparent to various light wavelengths.</p>
<p>-substance for example such as (d-1 lactide-glycolide) copolymer when used as an extra coating to the dots alters the lifetimes of the dots because it makes them resist enzymic degradation more.Improved smoothness of the dots may be done by annealing the polymer coats,this improves the flow of the dots through the * veins,arteries and capillaries in the body.Stabilization of the polymer coats may also be done to increase the lifetimes of the dots in the body by mixing them with substances such as Dextran 12.000 or polysorbate 85.</p>
<p>Other polymer substances usable may be poly(alkylene glycol), methoxypolyethylene glycol, ethoxypolyethylene glycol, polyethylene oxide, propane-co-sebacjc anhydride, co polymers of polyoxyethylene and polyoxypropylene and mixtures of the above may be used as polymer coats.</p>
<p>Dyes that may be used are suggested as the following:-Near infra-red fluorescent dye Indocyanine green(I.C.G.)Red dye Rhodamine(WT),yellow green dye (Fluorescein) and dye Bodipy.</p>
<p>All of the above are non-toxic, biodegradable,fluorescen dyes.</p>
<p>Many more dyes that fluoresce at differing wavelengths of exciting light sources may be used for different dots Trace elements that are non toxic may be used to dope and hence colour the semi transparent polymer coat S.This allows further differentiation of dots, suggested ones are Na+ions,Ca2i-jons,K+ ions S atoms,Mg2+jons,phosphate ions3-etc The dot is described as a flattened egg shaped disc that is smooth surfaced.</p>
<p>The dots are now described with the aid of the accompanying drawings:-In figure 1 the semi-transparent outer biodegradable polymer layer is shown as number I.The inner fluorescent dye is shown as number 2.Transparent circular areas in polymer wall are 7.</p>
<p>in figure 2 light source 3 is illuminating the dye 2, the dashed arrows show light shining on through the transparent areas 7 and the consequent fluorescence(dashed arrows again) recorded by spectrophotometer,4.</p>
<p>In figure 2 the light source 3 has wavelenght emitting controls for recording what wavelengths it is emitting and at what luminosity.The spectrophotometer 4, picks up the dye's fluorescence and records it.A surrounding blood cell is 8.</p>
<p>The dot in figure 2 is shown as being surrounded by blood contents, example cells 8, plasma fluid etc it is distinguished from its environment because it fluoresces under the light source 3.The outer polymer coat 1 is transparent to the light 3 in the areas that are seen as transparent circular shapes 7 the other surface areas in the polymer coat 1, are doped and are semi-transparent 5.</p>
<p>The concentration of the drug in the blood may be estimated knowing the dot's concentration in the drug tablet(about 1 per cent) and the number of dots seen per square centimetre under the microscope during fluorescence.</p>
Claims (1)
- <p>Claims 1) A microbiodot that comprises an, outer, transparent to lightin parts, biodegradable, non toxic, polymer layer and an inner, non toxic, fluorescent dye layer.</p><p>2) A microbiodot as in claim 1 in which said dye layer is able to fluoresce under a given light source at a particular wavelength when illuminated by said light source.</p><p>3) Microbiodots as in previous claims above that have for differentiation purposes differing opacities,densities, dyes and biodegradable properties so that each said microbiodot differs recordably from each other for fluorescent recordings and lifetime in the human body.</p><p>4) A microbiodot that according to all previous claims is able to be administered into the human body by way of injection or orally, it's size being determined by ability to be absorbed by the villi of the small intestine and be part of the body's bloodstream or travel along veins to enter main bloodstream.</p><p>5) A microbiodot as in all previous claims that, under fluorescence of it's dye layer will be visible to scrutiny using an optical microscope and other optical instruments when present in the human bloodstream.</p><p>6) A microbiodot as in all previous claims that is used as a tag when mixed with a drug that is able to identify said drug when taken into the human body after fluorescent examination of it's dye's fluorescence using a spectrophotometer.</p><p>7) A microbiodot as in all previous claims that by means of dot count per square centimetre of observed human blood an estimation of a tagged drugs ingested concentration may be done.</p><p>8) A microbiodot as in all previous claims that has transparent circular areas in its polymer coat that are fully transparent to any illuminating Eight sources and the areas in this polymer coat that remain are doped with various trace elements that cause only partial emissions of fluorescing light from the inner fluorescing dye when said dye is illuminated.</p><p>9) A microbiodot as in all previous claims that may have nano particles of soft iron in the outer polymer layer to aid separation of said dot when in the blood sample when an applied magnetic field is used on a blood sample containing said microdot(s).</p>
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0616415A GB2440910A (en) | 2006-08-18 | 2006-08-18 | A marker for studying drug dynamics in vivo |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0616415A GB2440910A (en) | 2006-08-18 | 2006-08-18 | A marker for studying drug dynamics in vivo |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0616415D0 GB0616415D0 (en) | 2006-09-27 |
| GB2440910A true GB2440910A (en) | 2008-02-20 |
Family
ID=37081183
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0616415A Withdrawn GB2440910A (en) | 2006-08-18 | 2006-08-18 | A marker for studying drug dynamics in vivo |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2440910A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2184015A (en) * | 1985-12-11 | 1987-06-17 | Ceskoslovenska Akademie Ved | Preparation for the diagnosis of the transport function of salpinx |
| WO2001078087A2 (en) * | 2000-04-06 | 2001-10-18 | Luminex Corporation | Magnetically-responsive microspheres |
| US6319488B1 (en) * | 1995-10-11 | 2001-11-20 | Institut für Diagnostikforschung GmbH an der Freien Universität Berlin | Contrast medium for near infrared diagnosis |
| US20050019265A1 (en) * | 2003-07-25 | 2005-01-27 | Hammer Daniel A. | Polymersomes incorporating highly emissive probes |
-
2006
- 2006-08-18 GB GB0616415A patent/GB2440910A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2184015A (en) * | 1985-12-11 | 1987-06-17 | Ceskoslovenska Akademie Ved | Preparation for the diagnosis of the transport function of salpinx |
| US6319488B1 (en) * | 1995-10-11 | 2001-11-20 | Institut für Diagnostikforschung GmbH an der Freien Universität Berlin | Contrast medium for near infrared diagnosis |
| WO2001078087A2 (en) * | 2000-04-06 | 2001-10-18 | Luminex Corporation | Magnetically-responsive microspheres |
| US20050019265A1 (en) * | 2003-07-25 | 2005-01-27 | Hammer Daniel A. | Polymersomes incorporating highly emissive probes |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0616415D0 (en) | 2006-09-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |