CN108578409A - A kind of stratiform magnetic fluorescence nano assembling causing cancer cell nuclear explosion - Google Patents
A kind of stratiform magnetic fluorescence nano assembling causing cancer cell nuclear explosion Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/88—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing selenium, tellurium or unspecified chalcogen elements
- C09K11/881—Chalcogenides
- C09K11/883—Chalcogenides with zinc or cadmium
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Abstract
The present invention relates to a kind of stratiform magnetic fluorescence nano assemblings that can cause cancer cell nuclear explosion, it is characterized in that stratiform magnetic fluorescence nano assembling is using dextran magnetic layered composite hydroxide Fluorouracil Magnetic Atrigel as medicine, using water-soluble near-infrared ZnHgSe quantum dots as fluorescent tracer, assemble through electrostatic complex technique.The nanometer assembling of the present invention can start the swollen of cancer cell and die access, cause cell nuclear explosion and cytoclasis, the swollen morphological change for dying process of cell can be disclosed by cell imaging technology, the preparation process of the present invention is simple and direct, efficient, product has diagnosis and treatment integrated function, disclose cell it is swollen die mechanism and remove tumor focus in terms of have Special Significance and good application prospect.
Description
Technical field
The present invention relates to a kind of chemotheraping preparations, specially a kind of to pass through Fluorouracil Magnetic slow releasing pharmaceutical (dextran-
Magnetic layered double hydroxide-fluorouracil system, DMF) it is multiple with fluorescence quantum (QD)
What conjunction obtained can cause cancer cell nuclear explosion, the stratiform magnetic fluorescence nano assembling of cytoclasis.
Background technology
Physics targeting preparation is with viral vector, organic cation type compound, recombinant protein and inorganic nano-particle etc.
It is prepared as carrier, the attainable highest targeting target of institute is the organelles such as mitochondria, usually causes cancer cell with apoptosis shape
Formula is dead；It is limited to novel carriers development technique, the preparation for targeting nucleus is at home and abroad rarely reported.Magnetic layered compound hydrogen
Oxide (Magnetic layered double hydroxides, MLDH) integrates Fe (OH) from structurexParamagnetism with
The medicine sustained and controlled release function of LDH, energy intercalation assembling drug, lamina surface can be with elecrtonegativity optics or bioactive molecule electrostatic knots
It closes, with face diameter than big, positive electricity enrichment and the transhipment advantage for easily crossing over cell deep layer barrier, " dextran-magnetic
There is layered double hydroxide-fluorouracil " (DMF) drug delivery system special cell nucleus targeting to transport energy
Power and lethal effect to cancer cell.Optical probe is developed, its pharmacological mechanism of follow-up study and cell traffic process have important meaning
Justice.
" swollen to die " (oncosis) is to follow cell closely by the preceding dead state occurred after lethal damage, be it is a kind of with have
Not in the new form of cell death of apoptosis.It is the swollen generation died and bacterium infection, viral infection, pathologic process, related with environment
The many factors such as toxic reaction, drug toxicity and high-energy radiation it is related.The chemotherapeutics for being seen in document report causes cancer
Cell is swollen, and the phenomenon that dying, is more, but actually rare at present for the research of chemotheraping preparation initiation cancer cell death mechanism, a pass
The technical bottleneck of key is a lack of tracking pharmacological action process, shows the bioprobe needed for morphosis character mutation.It is existing
Phenotypic characterization technology is to carry out cell steady State Analysis using transmission electron microscope, and dynamic imaging tracking optical agents used are mostly fluorescence
Element or biological dye, these materials and the combination stability of drug or preparation, optical stability are limited, can not ideal, accurately
The morphologic information of targeting preparation chemotherapy mechanism is provided.
Invention content
The present invention is intended to provide a kind of can cause cancer cell is swollen to die and to the cell traffic of Nano medication itself and its can draw
Send out the stratiform magnetic fluorescence nano assembling that cancer cell nuclear explosion process carries out optics tracer.
The technical solution taken for achieving the above object is：
A kind of stratiform magnetic fluorescence nano assembling causing cancer cell nuclear explosion, it is characterised in that the stratiform magnetic fluorescence is received
Rice assembling be using dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic slowly released and controlled-drug delivery system as medicine,
Using water-soluble near-infrared ZnHgSe quantum dots as fluorescent tracer, assemble through electrostatic complex technique.
Dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic the Atrigel and water solubility are close
Infrared ZnHgSe quantum dots in mass ratio 1：1~1：3 is compound.
Dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic the Atrigel is using coprecipitated
(concrete technology can be found in Chinese patent ZL2009101173717 and Gou Guojing for solvent conversion technology synthesis in shallow lake-ion exchange-
Supramolecular Assembling characterization Deng " dextran-magnetic layered composite hydroxide-fluorouracil " drug delivery system and anxious toxicity water
It is flat, chemical journal, 2012,70 (2)：161~169).
Using water phase one pot process, concrete technology is the water solubility near-infrared ZnHgSe quantum dots：
A, by Zn (NO3)2With water dissolution, clarification, in N2Deoxygenation under circulation, room temperature and magnetic stirring condition, then according to mole
Compare Zn2+/Hg2+=1：0.03~0.06 ratio, by Hg (NO3)2Solution is added thereto, and is uniformly dispersed, according still further to molar ratio Zn2 +/ mercaptopropionic acid=1:Mercaptopropionic acid is added in 1.6~2.0 ratio, adjusts pH to 6.0~9.0 after reaction in-situ, Zn is made2 +-Hg2+Mercaptopropionic acid precursor solution；
B, Se/NaBH in molar ratio4=1:1.5~2.5 weigh Se powder and NaBH4Solid is dissolved in water, in N2Circulation, 40
Reaction to Se powder disappears under~50 DEG C of constant temperature and magnetic stirring condition, and NaHSe slurries are made；
C, Zn in molar ratio2+/ NaHSe=1：The hot slurries of NaHSe made from step b are added to by 0.125~1 ratio
Zn made step a2+-Hg2+Mercaptopropionic acid precursor solution, in N2It is reacted under protection, 80~100 DEG C of constant temperature and magnetic stirring condition
Fluorescence intensity to liquid phase no longer rises；
D, reaction paste is stood, after ageing, is added absolute ethyl alcohol sedimentation, separation, is abandoned or adopted supernatant, centrifuge, gained is solid
Phase sample is washed with absolute ethyl alcohol, vacuum drying.
In process a, the deoxygenation time is 30~40min, 30~60min of reaction in-situ time, adjusts pH with a concentration of
2.0mol·L-1NaOH solution.
In process d, the reaction paste standing, 60~80min of digestion time are washed 2~3 times with absolute ethyl alcohol, are centrifuged
Separation condition is room temperature, 4000~5000rpm, and vacuum drying condition is 65~80 DEG C, 0.085MPa；In process a and c, magnetic stirs
Mix rotating speed is 200~300rpm.
The electrostatic complex technique packaging technology process is：
A, by water-soluble near-infrared ZnHgSe quantum dots and dextran-magnetic layered composite hydroxide-fluorouracil
Magnetic Atrigel is according to 1:1~1:3 quality proportioning mixing is ground；
B, it is suspended with absolute ethyl alcohol, the made mixed-powders of dispersion steps a, then by suspension ultrasonic disperse, Magneto separate, from
The heart detaches, absolute ethyl alcohol washing, vacuum drying.
The ultrasonic disperse refers to that suspension is placed into ultrasonic water bath, in 30~50 DEG C of 1~3h of temperature ultrasonic disperse.
The Magneto separate refers to the magnetic solid matter in suspension after magnet adsorption ultrasonic disperse, tipping liquid phase, removing
Unbonded ZnHgSe quantum dots.
The absolute ethyl alcohol washing solid phase sample 2~3 times.
The vacuum drying condition is 50~60 DEG C, 0.085MPa.
The study found that the cancer cell death form that DMF causes has marked difference with common Apoptosis, in cellular morphology
" cell space expansion, cytosol are lost in for performance in terms of；Rough surfaced endoplasmic reticulum (RER) and golgiosome expansion；Mitochondria cohesion, subsequent swelling；Core
Chromatic agglutination；The characteristic feature of " cell is swollen to die " such as bubble or bubble of the formation without organelle in endochylema "；DMF has magnetic
Antitumor drug, can be transported to cancer cell core by targeting and the dual transport features of cell nucleus targeting, be played cancer cell most direct
Killing effect；The cell traffic process and intracellular biochemical reaction of DMF causes cancer cell dead in the form of " swollen to die ", to play
Eradicate the effect of internal canceration lesion；It causes the mechanism of cancer cell death and " film is impaired to be caused to die channel " and " mitochondrial oxidation
Stress cause to die channel " hypothesis has significant difference, particularity to show as causing cancer cell " nuclear explosion ".
It is suitble to be visited with the fluorescence needed for the online modes research DMF chemotherapy mechanism such as living cells imaging, living imaging to develop
Needle, the present invention selects excellent in optical properties, good water solubility, and can make fluorescent tracing with the near-infrared quantum dots of DMF stable bonds
The QD@DMF stratiform magnetic fluorescent nanometer particles with diagnosis and treatment integrated function are made through electrostatic complex technique in agent, and research is found
The assembling causes the special phenotype of cancer cell nuclear explosion.The cell nucleus targeting of the DMF@QD systems is transported and pharmacological action can start
The swollen of cell dies access, causes cancer cell nuclear explosion and cytoclasis；It can disclose that cell is swollen to die process by cell imaging technology
Morphological change, to study cell the swollen mechanism and clinical cure the root tumor focus of dying have significant application value.
The technical characterstic of the present invention is embodied in：DMF drugs in DMF@QD nanosystems can start the swollen of cancer cell
Access is died, effect initial stage causes cellular swelling, after birth permeability to increase, and the lasting invasion of a large amount of DMF particles causes organelle
Damage in various degree；Late nuclear swelling, explosion are acted on, cytoclasis is caused.Not only signable DMF particles invade damage to quantum dot
Organelle, initiation " cell is swollen to die " complete procedure, and can strengthen nucleus and cell membrane " explosion " energy and destroy effect
Fruit.
The preparation process of the DMF@QD nanosystems of the present invention is simple and direct, efficient, and product has diagnosis and treatment integrated function, is disclosing
There are Special Significance and good application prospect in terms of the Death Mechanism and removing tumor focus of cell.
The present invention can use in situ imaging technology and MTT experiment, detect the swollen of cancer cell and die.Wherein, living cells is imaged skill
Art condition and operating process are as follows：
Take exponential phase of growth human gastric cancer MGC-803 cell, with pancreatin digestion, centrifugation, be made cell suspension, be inoculated in it is sharp
(inoculation quantity 20 × 10 in the special ware of light co-focusing imaging4), at 37 DEG C, 5%CO2It is incubated for 24 hours in incubator.Respectively with containing
There are 1640 culture mediums of 10% fetal calf serum to prepare 0.6mgmL-1ZnHgSe quantum dots, 1.1mgmL-1DMF and 1.0
~1.6mgmL-1ZnHgSe@DMF complex solutions are stored in 4 DEG C of refrigerators, spare.Cell normally culture for 24 hours to after adherent,
It discards culture solution, with PBS strong flushings 3 times, adds 0.5mL culture solutions, will be copolymerized burnt ware through pass-through box takes living cells work
It stands microscope.Setting condition (sets 37 DEG C of living cells work station operating temperature, simulation incubator environment is for 5%CO2), with disposable
Suction pipe absorbs the culture solution for maintaining transfer, and the liquid that 2mL has been prepared is added.Before starting shooting, while transmission channels and glimmering are set
Optical channel, fluorescence channel select the laser of 575 ± 25nm, light intensity 32%；Transmission channels select the bandpass filtering of 632 ± 60nm
Device, light intensity 2%；Total duration 9h is shot, it is primary to be spaced the automatic shooting per 2min.
The method for detecting killing in vitro cancer cell effect is identical as routine MTT operating technologies, detailed in Example 3.
Description of the drawings
The XRD of Fig. 1 DMF@QD nano-particles；
The FT-IR of Fig. 2 DMF@QD nano-particles；
The TG of Fig. 3 DMF@QD nano-particles is characterized；
The TEM patterns of Fig. 4 DMF@QD nano-particles；
The Zeta potential of Fig. 5 DMF@QD nano-particles and variation；
Fig. 6 with the living cells of 1.4mg/ μ L concentration DMF@QD nano-particle incubated cell 7h gastric carcinoma cells MGC-803 at
As result；
Fig. 7 with the living cells of 1.2mg/ μ L concentration DMF@QD nano-particle incubated cell 7h gastric carcinoma cells MGC-803 at
As result；
Fig. 8 cancer cells MGC-803 is swollen die during the change curve of karyon and cell space diameter.
Specific implementation mode
Embodiment 1：Prepare mass fraction 1:3 DMF@QD stratiform magnetic fluorescence nano assemblies characterize sample physics and chemistry
Matter.
(1) water phase one pot process ZnHgSe quantum dots are used：
A, the Zn (NO of 0.5131g are weighed3)2·6H2O solids put into 1000mL reactors, and 900mL water dissolutions is added extremely to clarify,
In N2Deoxygenation 30min under circulation, room temperature and 300rpm magnetic stirring conditions；Zn in molar ratio2+/Hg2+=1：0.05 ratio takes 863 μ
Hg (the NO of L3)2·4H2O solution (0.01molL-1) be added in above-mentioned solution and be uniformly dispersed.Zn in molar ratio2+/ MPA=1:
The MPA of 22 μ L is added into above-mentioned mixed solution for 1.8 ratio, in situ under the conditions of react 50min, then, be added dropwise
2.0mol·L-1NaOH solution adjusts the terminal pH to 8.5 of slurries, Zn is made2+-Hg2+- MPA precursors；
B, Se/NaBH in molar ratio4=1:2 weigh 0.017g Se powder and 0.016g NaBH4Solid phase, input 100mL reactions
Device adds 10mL distilled waters, in N2Reaction to Se powder disappears under circulation, 45 DEG C of constant temperature and 300rpm magnetic stirring conditions, is made
NaHSe；
C, Zn in molar ratio2+/ NaHSe=1：Step a institutes are added in the hot slurries of NaHSe made from step b by 0.125 ratio
The Zn of system2+-Hg2+In-MPA precursor solutions, in N2It is reacted to liquid phase under protection, 100 DEG C of constant temperature and 300rpm magnetic stirring conditions
Fluorescence intensity no longer rises；
D, reaction paste stand, ageing 60min after, add absolute ethyl alcohol sedimentation, separation, abandon or adopt supernatant, room temperature,
Centrifuged under the conditions of 5000rpm, after gained solid phase sample washs 2~3 times with absolute ethyl alcohol, be placed in 65~80 DEG C,
It is dried in 0.085MPa vacuum drying chambers.
(2) DMF@QD nano-complexes are prepared：0.006g ZnHgSe and 0.002g DMF solid phase samples are weighed, agate is placed in
It in Nao mortars, mixes well, polish 45min；It is suspended with absolute ethyl alcohol, the solid powder of dispersion polishing mixing, suspension is put
It sets in ultrasonic water bath, in 45 DEG C of temperature ultrasonic disperse 70min；Magneto separate is carried out while hot, removes unbonded ZnHgSe quantum
Point.Disperseed again with ethyl alcohol, ultrasound, Magneto separate, is then centrifuged under the conditions of room temperature, 5000rpm, solid phase is washed with absolute ethyl alcohol
After sample 2~3 times, it is placed in 60 DEG C, dries in 0.085MPa vacuum drying chambers.
(3) object phase is carried out to synthetic sample and physicochemical property characterizes.With Rigaku D/max-rB XRD-6000 diffractometers
(Cu K α, λ=0.15406nm) detects the XRD spectrums of sample under the conditions of 40kV, 30mA.With German Brooker company's T ENEOR27
Type infrared spectroscopy spectrometer detects IR spectrum (KBr tablettings, the 4000cm of sample-1~400cm-1).With French SETARAM companies
SETSYS-1750CS type thermal analyzers make sample heat analysis (N2Atmosphere, 10 DEG C of min of heating rate-1, 30 DEG C~650 DEG C).With
Hitachi's H-7560B transmission electron microscopes characterize particle morphology, and ultrapure water-soluble sample takes a small amount of suspension to drip on copper mesh, is air-dried,
Accelerating potential 80kV, observation, shooting particle morphology under the conditions of 5~70,000 times of amplification.With Malvern (Malvern) laser particle analyzer
The Zeta potential of determination sample takes 1mL concentration >=0.5gL respectively-1Ultra-pure water solution, be added to measure Zeta potential it is special
In cuvette, same sample follow-on test is three times.
Embodiment 2：Prepare mass fraction 1:2 DMF@QD stratiform magnetic fluorescence nano assemblies；With 1.4mg/ μ L concentration
Human gastric cancer MGC-803 cells are acted on, living cells imaging is carried out.
(1) ZnHgSe quantum dots are prepared：Weigh the Zn (NO of 5.1313g3)2·6H2O solids put into 1000mL reactors, add
900mL water dissolutions are to clarifying, in N2Deoxygenation 30min under protection, room temperature and 300rpm magnetic stirring conditions, adds 8.6mL concentration
0.01mol·L-1Hg (NO3)2·4H2After mixing 30min, the MPA of 0.22mL, reaction in-situ is added dropwise in O solution, stir in situ
45min；Then, 2.0molL is added dropwise-1NaOH solution, control the terminal pH to 9.0 of slurries, Zn be made2+-Hg2+Before-MPA
Body.
Weigh 0.17g Se powder and 0.16g NaBH4Solid phase is put into 100mL reactors, adds 10mL distilled waters, in N2
Reaction to Se powder disappears under protection, 50 DEG C of constant temperature and 300rpm magnetic stirring conditions, and NaHSe is made.The hot slurries of made NaHSe are added
Enter Zn2+-Hg2+In-MPA precursor solutions, in N2It is reacted to liquid phase fluorescence under protection, 100 DEG C of constant temperature and 300rpm magnetic stirring conditions
Intensity reaches peak.Slurry stand, ageing 60min after plus absolute ethyl alcohol sedimentation, separation, abandon or adopt supernatant, room temperature,
It is centrifuged under the conditions of 5000rpm, after washing solid phase 2~3 times with absolute ethyl alcohol, is placed in 65 DEG C, dries in 0.085MPa vacuum drying chambers
It is dry.
(2) DMF@QD nanosystems are prepared：0.06g ZnHgSe solid phase samples and 0.03g DMF powder are weighed, agate is placed in
It in Nao mortars, mixes well, polish 30min.Then, it will grind, in finely dispersed solid suspension to 500mL absolute ethyl alcohols,
Suspension is placed into ultrasonic water bath, ultrasonic disperse 4h under the conditions of 30 DEG C.Hydrothermal solution Magneto separate, in magnet adsorption liquid phase
Magnetic solid matter, tipping liquid phase is to remove unbonded ZnHgSe quantum dots.Again dispersion, ultrasound, Magneto separate, then normal
Temperature centrifuges under the conditions of 5000rpm, after wash solid phase sample 2~3 times with absolute ethyl alcohol, is placed in 60 DEG C, 0.085MPa is dried in vacuo
It is dried in case.
(3) human gastric cancer MGC-803 cells are acted on 1.4mg/ μ L concentration, QD nanometers of DMF@is tracked with living cells work station
Particle causes cancer cell nuclear explosion, the swollen process died.
Take exponential phase of growth human gastric cancer MGC-803 cell, with pancreatin digestion, centrifugation, be made cell suspension, be inoculated in it is sharp
(inoculation quantity 20 × 10 in the special ware of light co-focusing imaging4), at 37 DEG C, 5%CO2It is incubated for 24 hours in incubator.Respectively with containing
There are 1640 culture mediums of 10% fetal calf serum to prepare 0.6mgmL-1ZnHgSe quantum dots, 1.1mgmL-1DMF and
1.4mg·mL-1ZnHgSe@DMF complex solutions are stored in 4 DEG C of refrigerators, spare.Normal culture for 24 hours to cell it is adherent after, abandon
It removes culture solution, with PBS strong flushings 3 times, adds 0.5mL culture solutions, will be copolymerized burnt ware through pass-through box takes living cells work station
Before microscope.Setting condition (sets 37 DEG C of living cells work station operating temperature, simulation incubator environment is for 5%CO2), with disposable
Suction pipe absorbs the culture solution for maintaining transfer, and the liquid that 2mL has been prepared is added.Before starting shooting, while transmission channels and glimmering are set
Optical channel, fluorescence channel select the laser of 575 ± 25nm, light intensity 32%；Transmission channels select the bandpass filtering of 632 ± 60nm
Device, light intensity 2%；Total duration 9h is shot, is automatically snapped at interval of 2min primary.
Embodiment 3：Prepare mass fraction 1:1 DMF@QD stratiform magnetic fluorescence nano assemblies；With 1.2mg/ μ L concentration
Act on human gastric cancer MGC-803 cells, living cells imaging tracking；The ability of killing in vitro cancer cell is evaluated with mtt assay.
(1) ZnHgSe quantum dots are prepared：Condition and technical process (identical as embodiment 2 (1))
A, the Zn (NO of 0.5131g are weighed3)2·6H2O solids put into 1000mL reactors, and 900mL water dissolutions is added extremely to clarify,
In N2Deoxygenation 30min under circulation, room temperature and 300rpm magnetic stirring conditions；Zn in molar ratio2+/Hg2+=1：0.05 ratio, takes
Hg (the NO of 862.5 μ L3)2·4H2O solution (0.01molL-1) be added in above-mentioned solution and be uniformly dispersed.Zn in molar ratio2+/
MPA=1:The MPA of 21.5 μ L is added into above-mentioned mixed solution for 1.8 ratio, in situ under the conditions of react 50min, then, drop
Add 2.0molL-1NaOH solution adjusts the terminal pH to 8.5 of slurries, Zn is made2+-Hg2+- MPA precursors；
B, 0.017g Se powder and 0.016g NaBH are weighed4Solid phase is put into 100mL reactors, and 10mL distilled waters are added,
In N2Reaction to Se powder disappears under circulation, 45 DEG C of constant temperature and 300rpm magnetic stirring conditions, and NaHSe is made；
C, by the hot slurries of NaHSe made from step b, the made Zn of step a are added2+-Hg2+In-MPA precursor solutions, in N2
The fluorescence intensity of reaction to liquid phase no longer rises under protection, 100 DEG C of constant temperature and 300rpm magnetic stirring conditions；
D, reaction paste stand, ageing 60min after, add absolute ethyl alcohol sedimentation, separation, abandon or adopt supernatant, room temperature,
Centrifuged under the conditions of 5000rpm, after gained solid phase sample washs 2~3 times with absolute ethyl alcohol, be placed in 65~80 DEG C,
It is dried in 0.085MPa vacuum drying chambers.
(2) ultrasonic disperse and electrostatical binding technology is used to prepare stratiform magnetic fluorescence compound ZnHgSe@DMF：
A, mass fraction QD is pressed:DMF=50%:50% proportioning weighs appropriate ZnHgSe quantum dots and DMF nanometers respectively
Drug, with agate mortar mixing, grinding 30min；
B, it is suspended, the made mixed-powders of dispersion steps a, suspension is placed into ultrasonic water bath, 40 with absolute ethyl alcohol
DEG C temperature ultrasonic disperse 3h；
C, with the magnetic solid matter in magnet adsorption liquid phase, tipping liquid phase is to remove unbonded ZnHgSe quantum dots.
Again dispersion, ultrasound, Magneto separate, then centrifuge under the conditions of room temperature, 5000rpm, solid phase sample 2~3 are washed with absolute ethyl alcohol
After secondary, it is placed in 50~60 DEG C, dries in 0.085MPa vacuum drying chambers.
(3) human gastric cancer MGC-803 cells are acted on 1.2mg/ μ L concentration, is received with living cells work station tracking magnetic fluorescence
Rice corpuscles causes cancer explosion, the swollen process died.
In addition to changing the concentration for testing drug used, other action conditions and operating process are the same as process (3) in embodiment 2.
(4) effect of tumour cell is acted on MTT experiment evaluation DMF@QD nanosystems
It is grouped by pharmaceutical agents such as ZnHgSe quantum dots, DMF and ZnHgSe@DMF, if blank control.Logarithmic growth phase
MGC-803 cells are made cell suspension with the culture solution containing 10% fetal calf serum, are inoculated in 96 orifice plates after pancreatin digests
(per 100 μ L of hole, containing 9000 cells), in 5%CO2, 37 DEG C are incubated for 24 hours.After cell covers with bottom hole, three groups of drugs of addition
Concentration gradient liquid (ZnHgSe gradients：2400μg·mL-1、1200μg·mL-1、600μg·mL-1、300μg·mL-1、150μg·
mL-1With 75 μ gmL-1；DMF gradients：800μg·mL-1、400μg·mL-1、200μg·mL-1、100μg·mL-1、50μg·
mL-1With 25 μ gmL-1；ZnHgSe@DMF are converted by DMF equivalent, are set corresponding concentration gradient).Every group of 6 multiple holes, if zeroing
Hole and control wells.In 5%CO2After 37 DEG C of atmosphere is incubated hour for 24 hours, add 20 μ L concentration 5mgml to every hole-1MTT solution, use
100 μ L culture solutions continue to cultivate.Culture solution is discarded after being incubated 4h, adds the DMSO of 150 μ L, is placed in low-speed oscillation 10min on shaking table.
The light absorption value OD in each hole is measured under 490nm wavelength with enzyme-linked immunosorbent assay instrument, calculates the growth inhibition ratio of cell.By improvement bandit
Formula method calculates IC50Value：
In formula：Xm、I、P、Pm、PnRespectively refer to lg maximum doses, lg (maximum dose/adjacent doses), positive reaction rate it
With maximum positive reaction rate, minimum positive reaction rate.Testing result refers to table 1.
The physicochemical property of DMF@QD nanosystems and its effect for causing cancer cell nuclear explosion
(1) material phase analysis and physicochemical property of sample
Fig. 1 provides the JCPDS standard cards such as the XRD and identification 32-0665 and 13-0088 used of sample.Wherein, 32-
0665 is the standard diagram of cubic zinc blende crystal form, and 13-0088 represents R- hexagonal crystal systems [Fe3.6Fe0.9(O,OH,Cl)9] type LDH
The XRD features of layered crystal are the important evidences of DMF Discriminating materials.ZnHgSe@DMF show relatively apparent quantum dot and spread out
Peak is penetrated, and MLDH diffraction does not protrude, and only sees the faint diffraction of (006) (23.55 °, 0.377nm).Because of characterization sample used
From embodiment 1, the ratio between the amount of substance of quantum dot and DMF in raw material for preparing is 3:1, DMF proportion it is very little (embodiment 2,
The MLDH diffraction enhanced imagings of 3 made samples)；In addition, it is chimeric by the outer layer of surface layer DET organic composites and quantum dot, to MLDH crystalline phases
There is masking action.The crystalline phase feature of ZnHgSe and part MLDH is presented in ZnHgSe@DMF particles, it was demonstrated that quantum dot is on the surfaces DMF
Success is chimeric, grafting.
Fig. 2 is the IR spectrum of sample, 3413,1647,1558cm-1Mark position shows the IR of ZnHgSe quantum dots respectively
It absorbs；In DMF structures, the stretching vibration of hydroxyl is from 3413cm-1Red shift is to 3421cm-1Place；Quantum dot ligand carbonylic stretching vibration
νC=OFrom 1647cm-1Peak is blue shifted to 1637cm-1, 1558cm-1Peak area becomes smaller, and prompts quantum dot and DMF that part hydroxyl may occur
Carboxylic is condensed.1109cm-1The 1013cm for being absorbed as DMF at place-1The red shift at peak corresponds to hydroxyl carbon-oxygen bond ν in DMF surface DETC-OH's
Vibrate mould (1160~1013cm-1)；Appear in 616cm-1、485cm-1IR absorb be DMF middle plate Lattice Oxygens stretching vibration
νM-O.IR analyses provide polyfunctional group in sample and deposit, the information that quantum dot is combined with DMF.
The heat flow curve and TG curves of sample are provided by Fig. 3.Shown in TG curves, the performance of DMF@QD compound thermal decomposition processes
Three zero-g periods.Weightlessness is in 30~132 DEG C of sections, heat content 90.66Jg for the first time-1, weightlessness 4.4%, category dehydration weightlessness.The
Secondary weightlessness is in 228~348 DEG C of sections, total weight loss 10.48%；DSC exothermic process is decomposed into front and back two with 304.8 DEG C for boundary
In the stage, this exothermic process is removed to be had outside the Pass with the MPA decomposition of quantum dot ligand, is also had with organic principle FU and DET decomposition contained by DMF
It closes.Endothermic decomposition twice occurs after 350 DEG C, it is related to the disintegration of quantum dot framework.By itself and slow endothermic decomposition process hereafter
Merge, total weight loss 13.41% (350~650 DEG C).The weightlessness of phase III is also wrapped in addition to the endothermic decomposition of quantum dot framework
Include endothermic decomposition (the heat absorption enthalpy 5.46Jg of the endothermic decomposition of MLDH stratiforms framework and LDO-Organics compounds in DMF-1,
460~492 DEG C) etc. processes；Exothermic process is then related with the recombination of quantum dot and DMF remnants and deep decomposition.
Fig. 4 is the transmission electron microscope picture of 2 made sample of embodiment.Sample particle is in condensed state, and reunion is close each other, divides
Divergence is low, but pedestal particle shape and quantum dot chimerism are high-visible.Wherein, pedestal particle size differs, and diameter is 30
Between~100nm, there are hexagonal features (wherein, to have the particle of evaluation of markers, the length of side 23nm of hexagon pedestal, diameter is about
46nm can represent the average level of different particles in figure), mostly in oval spherical；Quantum dot is uniformly inlayed, is incorporated in DMF bases
Embedded combination feature is presented in frame surface, apparent to the electrostatical binding trend of MLDH laminates；Considerable diameter about 6nm is Multiple-quantum
Point reunion state.TEM pictures provide the ocular proof that nanoscale quantum dot is combined with DMF particles in synthetic sample.
Zeta potential influences the biotransport and application performance of nano-particle.Using 2 made sample of embodiment as test object,
ZnHgSe, the Zeta potential of DMF and ZnHgSe@DMF particles and its variation occurred with concentration are investigated, the results are shown in Figure 5.In
In property solution, the Zeta potential of quantum dot is basically unchanged；The Zeta potential of DMF and ZnHgSe@DMF is with particle concentration from 50mg
L-1Increase to 500mgL-1Significant changes occur, DMF increases to 9mV from -2mV, in 200mgL-1It remains unchanged later, and
ZnHgSe@DMF increase (being converted to negative value) in parabolic variation with particle concentration.When particle concentration is from 50mgL-1Increase to
70mg·L-1When, the Zeta potential of ZnHgSe@DMF is increased to -13.5mV from -23.87mV；In 70mgL-1To 100mgL-1
Concentration ranges substantially remain in -13.5mV or so；Concentration about 300mgL-1Later, Zeta potential is moved to the increased direction of negative value
It is dynamic.Quantum dot and MDF particles are presented the colloidal particle stability in Bu Tong electrical section, and the current potential of compound particle is in the areas Fu Ban (between two
Between person), far from 300mgL-1Concentration range in have enough colloidal stabilities.
(2) DMF@QD nano-particles cause the in situ imaging result of MGC-803 cancer cell nuclear explosions
Fig. 6 provides tri- kinds of particles of ZnHgSe, DMF and ZnHgSe@DMF and the work of MGC-803 cell interaction processes is thin
Born of the same parents' real time imagery result.Fig. 6 A-a are shown, act on initial stage in pure quantum dot, cell growth state is good, and quantum dot can not advise greatly
Mould invades cell；After acting on 12min, quantum dot is hovered between cell, and individual (arrow instructions) is adhered to cytoplasma membrane, sends out
Faint red fluorescence, the form and active state of most cells are normal；Until when effect 328min, quantum dot appears in a
In the cytoplasm of other cell, but cell keeps the vigor such as normal morphology and rejection, movement (Fig. 6 A-c)；After acting on 420min, cell
There is the toxic reaction to quantum dot, many cells start to be rounded (total volume contraction), and main body is shunk in cell space；Performance is to quantum
The phenomenon that point rejects, squeezes out cell space from cytoplasm (Fig. 6 A-d).The above phenomenon illustrates that cell is weak to the affinity of simple quantum dot, arranges
The opposite sex is strong, tolerance time is long；Quantum dot can only cause the metamorphosis of cell space, can not cause cell nuclear explosion.
The effect of DMF particles and cell is fast, strong, and initial stage contacts defense reaction and the rejection-for causing cell quickly
Black particles stream is discharged from after birth spout around cell space periphery, granule or hovers between several cells, it was demonstrated that the particle energy
It is strong to enter cell space initiation intramicellar reaction, after birth compatibility quickly；Organelle movement is active, cell keeps normal morphology (Fig. 6 B-
a).When acting on 80min, cell still keeps the rejection to DMF particles and defense reaction ability, but enters the particle of cell space early period
Toxic reaction-organelle, nucleus and the kernel swelling inside cytoplasm, karyon and cell space is caused to be rounded (figure B-b).Effect is extremely
When 260min, the black particles quantity of the discharge in cellular rejection reaction aggravation-cell peripheral environment increases, and cell shoots out
Behavior, cytoplasmic organelle particle Showed Very Brisk；The cytoplasm extreme expansion of arrow meaning cell, karyon film inner circumferential and kernel periphery are visible black
Color tablets subflow (Fig. 6 B-c).After 1 hour again (effect 320min), arrow meaning cell (is expanded to the thin of the limit in a upper figure
Born of the same parents) it explodes from karyon edge, the cell space on right side is completely severed, slurries are all lost in；Other cells, some also begin to drastically
Expansion, some continue to keep rejection.
Fig. 6 C-a show, it is swift and violent that QD@DMF particles cause the swollen effect died of cancer cell, camera shooting initial stage (about 10 after dosing~
15min) there is red fluorescence particle to appear in plasma membrane and the core week of respective cells；Defense reaction behavior has been presented in cell, but big
The form of part cell is normal, and existing state is good.When effect is to 195min, about 50% cell starts to explode, by karyon
Start from center to after birth border extension；The cell membrane convex drum of arrow meaning, formation are free of organelle in Fig. 4 C-b
Vesicle, the significant change of permeability of cell membrane before display karyon explosion.Continue after ten minutes (when overall length 205min), it is more thin
Born of the same parents' spalling, the karyon of middle right part cell collapses, cell space fragmentation, kernel distribute strong red fluorescence；Signified thin of Fig. 6 C-c arrows
Born of the same parents, it is extracellular still to have the positive fast strikethrough after birth of QD@DMF particles, into cytoplasm, show that cell space swelling aggravates with after birth permeability
Parallel process.Again after 30 minutes (when effect 245min), which, which finally occurs nuclear explosion, makes red fluorescence spread all over entirely carefully
Born of the same parents show to have contained a large amount of QD@DMF particles in cytoplasm and nucleus, and Fig. 6 C-c illustrations show the cell in 255min,
Karyolysis, swollen quick-fried and blast wave burst entire cell, cause after birth rupture, the slurries with red fluorescence to extracellular outflow
The phenomenon that.
Fig. 7 provides fixed point tracking nano-particle in embodiment 3 and causes single cancer cell swelling up to karyon blast process
Imaging results.Capture 8 pictures prove, subject cell show to nano-particle phagocytosis, rejection exocytosis, cell space expansion,
The different phase of karyon dissolving, karyon explosion and cytoclasis.Fig. 7 A, B show that nano-particle can complete cell in 15min
It is internalized by, into endochylema, cell immediately shows the act of defense being persistently internalized by particle and the reaction of rejection exocytosis, in 80min
Cell still maintains the normal physiological reaction such as exocytosis, but apparent swelling trend has occurred in karyon, it was demonstrated that nano-particle has been enter into
Karyon simultaneously causes strong pharmacological reaction and cell space stress reaction.In 145~275min periods, organelle and cell space it is swollen
Swollen trend constantly enhances；Hereafter, nucleus explosion, karyon content spray from inside to outside, break through after birth constraint rapidly；340
The sections~470min, the explosion amplitude and jet space of karyon constantly expand, until karyon almost produces after birth when 470min
The also all leakages therewith of notch, cellular content and organelle, final cell space, which is disintegrated, cell is swollen dies.Fig. 8 provides nano-particle and draws
Play the diameter change curve of cancer cell nuclear explosion process cell space and nucleus.Wherein there are 3 important timing nodes, when with
170min is boundary, and cell space reaches a plateau by lasting swelling, hereafter, expands again and reaches volume when 192min
Hereafter maximum value is immediately shunk, definite value is maintained since 240min, up to nuclear explosion terminates.Karyon diameter experienced first half
Hour stabilization and 60min before increase outside, present the fluctuation of about ± 1220nm amplitudes in the sections 50~239min, reflection with
The active physiological reaction such as deformation and contraction, expansion of nucleus in nano-particle mechanism；Using 239min as boundary, karyon exists
It completes last time in extremely short time interval (about 60s) to shrink, after deformation, moment starts explosive expansion, and volume increases rapidly
It is long, after the plateau for maintaining about 30min, start lasting extension, until cell space is disintegrated, nuclear explosion terminates.
(3) DMF@QD nano-particles act on the MTT results of MGC-803 stomach cancer cells
MTT experiment shows that quantum dot, DMF and ZnHgSe@DMF increase the cell of human gastric cancer MGC-803 cytosiies for 24 hours
It grows inhibiting rate to increase with sample concentration and increase, is in effect-amount correlation, there is notable significant difference (P ＜ 0.01).Same
After acting on same time under concentration, ZnHgSe@DMF are higher than ZnHgSe, DMF to the proliferation inhibition rate of cell, prompt it is clinical with compared with
Low dose of ZnHgSe DMF can get preferable curative effect.Each sample is calculated to gastric cancer cell line MGC-803 by bandit's formula formula
IC50It is worth (table 1).Wherein, the IC of ZnHgSe50Value is maximum, and toxicity is relatively minimum, and the cytotoxicity of unit mass DMF is about
2.6 times of quantum dot.The cancer cell toxicity of DMF is related with the antitumor drug of system load and release, and MLDH carriers are to specific
Organelle may also generate certain effect；It is most important the reason is that DMF has superpower cell traffic ability and cell nucleus targeting
Can, so that the drug fluorouracil of delivery is generated most direct killing effect to cancer cell, and the cytotoxicity of quantum dot only with its
Metal is related.The IC of ZnHgSe@DMF50Value is minimum, and cancer cell toxicity is most strong, and Nano medication and quantum dot is presented
Superposition, i.e., in addition to DMF, electrostatical binding when the ZnHgSe quantum dots on the surfaces DMF are in stabilizer mercaptopropionic acid partial exfoliation,
Hg2+Plasma diffusing W,Mo can also cause cancer cell additional toxicity.Therefore, the cancer cell toxicity of compound is with DMF drugs and because of DMF
The practical intake of quantum dot increases caused by transmission and its intracellular metabolism is related.
IC of 1 different pharmaceutical of table to MGC-803 cells50Value
The above Cell Biology Experiment shows individual quantum dot cellular change low to the toxicity of cancer cell, caused
It is only limitted to proliferation activity to die down, but the structure of the organelles such as cell membrane and nucleus keeps complete；When DMF acts on cell, carefully
Simultaneously after birth rupture occurs for the swelling of born of the same parents' device.But the fluorescent marker of quantum dot makes DMF@QD cause the swollen metamorphosis mistake died of cancer cell
Journey shows very clear, complete that cell nuclear swelling, expansion is presented in cell, push cytoplasm, until burst entire cell this
Complete nuclear explosion process.This is the coefficient result of DMF all composite parts of@QD systems.There is no apparent for quantum dot
Cytotoxicity and cell fusion, transhipment advantage, but the electrostatical binding of it and DMF are further enhanced DMF and are killed in a manner of " swollen to die "
It goes out the ability of cancer cell, synergistic effect is presented；The participation of quantum dot obviously strengthens DMF to organelle, particularly to nucleus
Destructiveness and energy " outburst " intensity.The above results show that DMF@QD are in clinical treatment, bio-imaging and cell " swollen to die "
Great application prospect in terms of mechanism study.
Claims (11)
1. a kind of stratiform magnetic fluorescence nano assembling causing cancer cell nuclear explosion, it is characterised in that the stratiform magnetic fluorescence nano
Assembling be using dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic slowly released and controlled-drug delivery system as medicine, with
Water-soluble near-infrared ZnHgSe quantum dots are fluorescent tracer, are assembled through electrostatic complex technique.
2. the stratiform magnetic fluorescence nano assembling as described in claim 1 for causing cancer cell nuclear explosion, it is characterised in that described
Dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic slowly released and controlled-drug delivery system and water-soluble near-infrared ZnHgSe
Quantum dot in mass ratio 1：1~3 is compound.
3. the stratiform magnetic fluorescence nano assembling as described in claim 1 or 2 for causing cancer cell nuclear explosion, it is characterised in that institute
Dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic slowly released and controlled-drug delivery system is stated to hand over using co-precipitation-ion
Change-solvent conversion technology synthesis.
4. the stratiform magnetic fluorescence nano assembling as described in claim 1 or 2 for causing cancer cell nuclear explosion, it is characterised in that institute
Water-soluble near-infrared ZnHgSe quantum dots are stated using water phase one pot process, concrete technology is：
A, by Zn (NO3)2With water dissolution, clarification, in N2Deoxygenation under circulation, room temperature and magnetic stirring condition, then according to molar ratio Zn2 + / Hg2+ = 1 ：0.03 ~ 0.06 ratio, by Hg (NO3)2Solution is added thereto, and is uniformly dispersed, according still further to molar ratio Zn2+
/ mercaptopropionic acid=1:Mercaptopropionic acid is added in 1.6 ~ 2.0 ratio, adjusts pH to 6.0~9.0 after reaction in-situ, is made
Zn2+-Hg2+Mercaptopropionic acid precursor solution；
B, Se/NaBH in molar ratio4 = 1 :1.5 ~ 2.5 weigh Se powder and NaBH4 Solid is dissolved in water, in N2Circulation, 40
Reaction to Se powder disappears under ~ 50 DEG C of constant temperature and magnetic stirring condition, and NaHSe slurries are made；
C, Zn in molar ratio2+/ NaHSe = 1 ：The hot slurries of NaHSe made from step b are added to by 0.125~1 ratio
Zn made step a2+-Hg2+Mercaptopropionic acid precursor solution, in N2Reacted under protection, 80 ~ 100 DEG C of constant temperature and magnetic stirring condition to
The fluorescence intensity of liquid phase no longer rises；
D, reaction paste is stood, after ageing, is added absolute ethyl alcohol sedimentation, separation, is abandoned or adopted supernatant, centrifuges, gained solid phase sample
Product are washed with absolute ethyl alcohol, vacuum drying.
5. the stratiform magnetic fluorescence nano assembling as described in claim 4 for causing cancer cell nuclear explosion, which is characterized in that process
In a, the deoxygenation time be 30 ~ 40 min, 30~60 min of reaction in-situ time, adjust pH with a concentration of 2.0 mol ×
L-1NaOH solution.
6. the stratiform magnetic fluorescence nano assembling as described in claim 4 for causing cancer cell nuclear explosion, which is characterized in that process
In d, the reaction paste standing, 40 ~ 80 min of digestion time are washed 2~3 times, centrifugation condition is with absolute ethyl alcohol
Room temperature, 4000 ~ 5000rpm, vacuum drying condition are 65~80 DEG C, 0.085MPa；In process a and c, magnetic speed of agitator is 200
~ 300rpm。
7. the stratiform magnetic fluorescence nano assembling as described in claim 1 for causing cancer cell nuclear explosion, which is characterized in that described
Electrostatic complex technique packaging technology process is：
A, by water-soluble near-infrared ZnHgSe quantum dots and dextran-magnetic layered composite hydroxide-Fluorouracil Magnetic
Slowly released and controlled-drug delivery system is according to 1:1~1:3 quality proportioning mixing is ground；
B, it is suspended with absolute ethyl alcohol, the made mixed-powders of dispersion steps a, then by suspension ultrasonic disperse, Magneto separate, centrifugation point
From, absolute ethyl alcohol washing, vacuum drying.
8. the stratiform magnetic fluorescence nano assembling as described in claim 7 for causing cancer cell nuclear explosion, which is characterized in that described
Ultrasonic disperse refers to that suspension is placed into ultrasonic water bath, in 30~50 DEG C of 1~3 h of temperature ultrasonic disperse.
9. the stratiform magnetic fluorescence nano assembling as described in claim 7 for causing cancer cell nuclear explosion, which is characterized in that described
Magneto separate refers to the magnetic solid matter in suspension after magnet adsorption ultrasonic disperse, tipping liquid phase, remove it is unbonded
ZnHgSe quantum dots.
10. the stratiform magnetic fluorescence nano assembling as described in claim 7 for causing cancer cell nuclear explosion, which is characterized in that institute
State absolute ethyl alcohol washing solid phase sample 2~3 times.
11. the stratiform magnetic fluorescence nano assembling as described in claim 7 for causing cancer cell nuclear explosion, which is characterized in that institute
It is 50~60 DEG C, 0.085MPa to state vacuum drying condition.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020083300A1 (en) * | 2018-10-24 | 2020-04-30 | 宁夏医科大学 | Magnetically-responsive thermally-sensitive fluorescent micelle particle and preparation method therefor |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104449661A (en) * | 2014-10-31 | 2015-03-25 | 苏州大学 | Novel information processing method based on DNA controlled quantum dots |
-
2018
- 2018-05-25 CN CN201810545545.9A patent/CN108578409A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104449661A (en) * | 2014-10-31 | 2015-03-25 | 苏州大学 | Novel information processing method based on DNA controlled quantum dots |
Non-Patent Citations (4)
| Title |
|---|
| MIN ZHANG, ET AL.: "Preparation and characterization of magnetic thermosensitive fluorouracil micelles", 《JOURNAL OF BIOMATERIALS SCIENCE》 * |
| QINYU PEI, ET AL.: "Recombination of CdHgTe Quantum Dot and "Dextran – Magnetic Layered Double Hydroxide - Fluorouracil" System for Cell Imaging", 《MATERIALS SCIENCE FORUM》 * |
| XUEQIN JIN, ET AL.: "Synthesis and Cell Imaging of a Near-Infrared Fluorescent Magnetic "CdHgTe–Dextran-Magnetic Layered Double Hydroxide–Fluorouracil" Composite", 《JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| 苟国敬等: ""右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶"给药系统的超分子组装与磁靶向缓释作用", 《功能材料信息》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020083300A1 (en) * | 2018-10-24 | 2020-04-30 | 宁夏医科大学 | Magnetically-responsive thermally-sensitive fluorescent micelle particle and preparation method therefor |
| AU2019366621B2 (en) * | 2018-10-24 | 2022-06-02 | Ningxia Medical University | Magnetically-responsive thermally-sensitive fluorescent micelle particle and preparation method therefor |
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