CN106806904A - A kind of lung cancer-targeted low toxicity quantum dot preparation - Google Patents
A kind of lung cancer-targeted low toxicity quantum dot preparation Download PDFInfo
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- CN106806904A CN106806904A CN201510847288.0A CN201510847288A CN106806904A CN 106806904 A CN106806904 A CN 106806904A CN 201510847288 A CN201510847288 A CN 201510847288A CN 106806904 A CN106806904 A CN 106806904A
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Classifications
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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
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
- A61K49/0067—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle quantum dots, fluorescent nanocrystals
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
-
- 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
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Materials Engineering (AREA)
- Nanotechnology (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract
The present invention relates to biotechnology and nano meter biomaterial field, the preparation of quantum dot preparation that be related to a kind of hypotoxicity, that pulmonary cancer diagnosis can be used for and application thereof.With lung cancer targeting molecule be connected traditional quantum dot by the present invention, constitutes composition or preparation with cell autophagy adjusting control agent afterwards.Especially the quantum dot preparation is made up of one or more lung cancer-targeted quantum dot with one or more cell autophagy/reinforcing agent.The features such as there is obtained quantum dot preparation of the invention toxicity to be less than general quantum dot preparation and selectively targeted lung cancer.The preparation process is simple of said preparation, applicability is wide, can be used for the production of large-scale.Further said preparation is primarily useful for preparing the preparation of diagnosis, treatment and detection lung cancer and other tumours.Simultaneously can be used for preparing spike and the location preparation of interior tumor cell.
Description
Technical field
The invention belongs to biotechnology and nano meter biomaterial field, it is related to a kind of low toxicity quantum dot of selectively targeted lung cancer
Preparation and application thereof, more particularly relate to the new lung cancer-targeted quantum dot and preparation method thereof and its with thin one or more
Born of the same parents' autophagy inhibitor is made new quantum dot preparation or composition, so as to reduce the toxicity of traditional quantum dot preparation.
Background technology
Data shows that lung cancer is one of global most common malignant tumour, and it is the first that its case fatality rate occupies malignant tumour.Due to
80% patients with lung cancer belonged to middle and advanced stage, was only capable of carrying out palliative treatment when medical, causes existence often without Special Clinical Manifestation early stage
Time is very short；And 5 years survival rates of the early stage of lung cancer (IA phases) are more than 70%, research display is many reason for lung cancer finds later,
But the main effective method of early diagnosis being a lack of for people at highest risk, therefore, develop new method of lung cancer diagnosis undoubtedly just into
The most important thing of effective foundation is provided for the early diagnosis for lung cancer.
At present, fluorescent microscopic imaging is that one kind sensitively carries out cancer cell diagnostic method, particularly cancer cell is developed early
Phase is diagnosed most development potentiality and the most widely used imaging technique, and the technology has that sensitivity is high, lossless, clinical peace
Complete and operating technology is simple, it is with low cost the characteristics of.The sensitivity of label and stability are using optical image technology pair
Cancer cell diagnosis is successfully crucial.In the past few decades, fluorescent labelling techniques turn into a kind of important biomarker technology.
It is own through in biomedical many fields, particularly being obtained in imaging cancerous and mark as label by the use of fluorescent dye
It is widely applied.Had many advantages compared with other labels such as radioactively labelled substance.But with entering for research
Exhibition, it is desired to which detection sensitivity is further improved, fluorescent dye is because its labeling effciency is low, photostability is poor and relatively low glimmering
The shortcomings of luminous intensity, has limited its development and application in the field.The label for growing up therewith is fluorescence nano
Particle such as quantum dot etc., the shortcomings of due to the photostability for which overcoming fluorescent dye poor and relatively low fluorescence intensity, into
It is the label that a new generation is most promising.
Quantum dot (quantum dot, QD) can be described as semiconductor nanocrystals body (semiconductor again
), nanocrystal quantum dot (quantum dot, QD) can be described as semiconductor nanocrystals body (semiconductor again
nanocrystal),.More mainly CdX (X=S, Se, Te) is studied at present.Quantum dot due to particle diameter very little (about 1~
100nm), electronics and hole be by quantum confinement, continuously can band become the discrete energy level structure with molecular characterization, therefore light scholarship and moral conduct
It is with some macromoleculars (for example:Polycyclic aromatic hydrocarbon) it is much like, fluorescence can be launched.The volume size of quantum dot is strictly controlled
Its light absorbs and emission characteristic.Research display, crystal grain is smaller, and specific surface area is bigger, is distributed in the atom on surface just
It is more, and the light activated positive electron on surface or negatron are bigger by the constraint effect of passivated surface, its dissimulated electricity can be just
Higher, the luminous energy of absorption is also higher, that is, there is quantum size effect (quantum size effect), so that its absorption band
Blue shift, fluorescent emission peak position also corresponding blue shift.Studies have reported that, single quantum dot particle is easily subject to impurity and lattice defect
Influence, fluorescence quantum yield is very low, but when with it as core, being coated with another semi-conducting material, forms core-shell structure copolymer
(core-shell) after structure, so that it may which quantum yield brought up into about 50%, even more high, and have several times on extinction coefficient
Increase, thus have very strong fluorescent emission.The nano particle of the nucleocapsid structure for having synthesized at present has, CdS/Ag2S、CdS/Cd
(OH)2, CdS/ZnS, ZnS/CdSe, ZnSe/CdSe, CdS/HgS, CdS/PbS etc. and sandwich construction CdS/HgS/CdS.
Quantum dot than organic fluorescence molecule stabilization, it can undergo it is repeated multiple times excite, be not susceptible to fluorescent bleach, therefore for research is thin
Interaction long-term between biomolecule provides powerful in born of the same parents.
In view of its unique Photophysics, quantum dot is widely used in cell in vitro mark.Have compared to traditional
Machine fluorescent dye, the main advantage of quantum dot is that it has stronger bleach-resistant performance (from a few minutes to a few houres), higher
Extinction coefficient (0.5~5 × 106L/(mol·cm- 1)) and quantum yield.Had by the quantum dot-labeled image for obtaining more preferable
Contrast and definition, therefore, it is possible to substitute organic dyestuff in most of fields.In recent years, quantum dot is used for intracellular imaging
Larger progress is achieved, many living cells and the intracellular component of fixation and albumen are by quantum dot-labeled, imaging, such as cell
Core, mitochondria, micro-pipe, microfilament protein, Cytokeratin and endocytosis body etc.；Meanwhile, quantum dot is also used for studying cell membrane egg
White and acceptor, including PSMA (PSMA), HER kinases, Glycine Receptors, thrombocytin transport protein, p- sugar
Albumen, the albumen of Band III and sodium-potassium ATPase etc.；Its most advantageously micro quantum dot in immunofluorescence application is with regard to energy
Enough produce detection signal；Studies have reported that quantum dot has flickering phenomenon in cell sample, it is referred to as " flicker ", the spy
Immunofluorescence test sensitivity can be brought up to single molecules level by property.
Quantum dot is because with Near-infrared luminescence, long-time stability, high brightness fluorescent, anti-light Bleachability etc. unique
Advantage makes them turn into the prioritizing selection of in vivo fluorescence imaging and mark.Akerman groups, by sulfation targeting peptides connect
Quantum dot is expelled in canceration rat body, takes out histotomy, it is found that a large amount of polypeptide quantum dot probes are enriched in cancerous issue
(AkermanME,Chan W,Akkonmen LP.Proc.Natl.Acad.Sci.,2002.99(20):12617-21)；Kim is small
Quantum dot is injected separately into group subcutaneous, their directed movements to post lymph node of mouse and pig, is swashed by low energy near-infrared
Hair (5 × 10-3W/cm2) obtain fluorescence imaging (Kim S, the Lim Y, Soltese of pig lymph node 1cm depths
E.Nature.Biotechnology.2004 22:93-97)；Result of study is laid a good foundation for the in-vivo imaging of living animal,
For the accuracy of clinical medicine imaging, surgical operation provides foundation.
With updating for quantum dot synthetic technology, quantum dot is expected to turn into one of most potential fluorescent marker,
Especially in the application of active somatic cell marker field.But be not yet generalized in clinical practice, mainly due to quantum dot sheet in
Inside and outside all has certain toxicity；Study and show in the mechanism of quantum dot and cell, their surface chemistry group
Minimum micropore is caused to cell membrane, it is complete that this ion concentration difference and cell interior that may change intraor extracellular play protection cell
The macromolecular concentration of whole property and normal operation function；On the other hand, quantum dot may directly results in the interaction of cell
Apoptosis and cell autophagy, so as to kill cell.
RGD peptide is one section of short peptide sequence being made up of tri- amino acid of Arg, Gly, Asp, is many integrins of cell surface
Such as one of the β 1 of α 5, the β 1 of α 3, ligands specific of α v β 1, the adhesion between energy mediated cell and extracellular matrix is to demonstrate,prove at present
Bright most effective, most widely used rush adhesion small peptide, while also having certain signal transduction function.In recent years, acceptor shows
As technology is more and more paid close attention to as an important biomedical research tools by people.Tumor receptor imaging technology is
Can be combined with the receptor-specific of expression high in tumor tissues using the receptors ligand of radioisotope labeling, so as to show tumour
The spatial distribution of acceptor, density and affinity etc.；The technology affinity is high, specific good, tissue penetration strong point, can be
The tumor imaging of high-contrast is obtained in short period, and rarely has the property reaction of human immunity source [NanMA, etal.One-
stepDNA-programmed growth of luminescent and biofunctionalized
nanocrystals.Nature Nanotech.,2009,4:121-125.].Jung etc. marks the RGD peptide of saccharification with 99mTc,
The combination of the saccharification small peptide and endothelial cell of result display mark has acceptor quantity dependency characteristic [Jung KH, et
al.Favorable biokinetic and tumor-targeting properties of 99mTc-labeled
glucosamino RGD and effect of paclitaxel therapy[J].J.Nucl.Med.,2006,47(12):
2000-2007.]；Vivo biodistribution imaging display：This radiopharmaceutical is rapidly cleared in humans in blood, intake of the liver to it
Seldom, and tumour cell in height intake state；Tumor image is high-visible in videograph process；Zhang etc. [43] is by carboxyl, phonetic
Pyridine is coupled with c (RGDyK) and obtains BPy-RGD, then marks BPy-RGD to obtain 99mTc (CO) (3)-BPy-RGD with 99mTc.
BPy-RGD is hydrophilic, so having good affinity to integrin receptor, this hydrophily tacking agent can also be to tumour
The integrin alpha v beta receptor active of cell surface is adjusted fact proved, after carrying out receptor blocking injection 4h with c (RGDyK), swells
Knurl is substantially reduced to the intake of 99mTc (CO) (3)-BPy-RGD；C after result of study proof carboxyl and pyrimidine modification
(RGDyK) there is target function higher to tumour, therefore 99mTc (CO) (3)-BPy-RGD is expected to be received as integrin family α v β
A kind of new and effective target tumor developer of body.
Cell autophagy (autophagy) also known as II type programmed death (the programmed cell death of type II),
The phenomenon of " self-digestion " common in eucaryote body (cellular degradation), can decompose it is intracellular impaired or
Unnecessary organelle and albumen produce the small-molecule substances such as nucleotides, amino acid to synthesize new protein for cell, and can maintain
The stabilization of intracellular microenvironment；Research shows that it is close with the development relationship of various diseases, especially tumour.
The difference of lysosome intracavitary is transported to according to intracellular substrate, mammalian cell autophagy can be divided into three kinds of sides
Formula：The autophagy of big autophagy (macroautophagy), small autophagy (microautophagy) and molecular chaperones mediation
(chaperone-mediated autophagy,CMA).Big autophagy mainly has following characteristics：(1) evolution is rapid；(2)
The inducibility of autophagy；(3) batch is degraded；(4) non-selectivity phagocytosis；(5) conservative of autophagy.Other two kinds of autophagy with it is big from
That bites differs primarily in that：Small autophagy is lysosome membrane self-deformation, then wraps up the substrate in phagocyte slurry；And molecule companion
The autophagy of companion's mediation then can selectively protein degradation.The big autophagy (hereinafter referred to as autophagy) of overview and tumor development and
Treatment relation the most closely [Sridhar S,Botbol Y,Macian F,et al.Autophagy and disease:
always two sides to aproblem.J Pathol.2012；226(2):255-73.].
The big enable of autophagy process is divided into 4 stages：1. under the stimulation of some factors such as starvation, anoxic, interfering effects of drug, from
The double membrane structure for biting bubble starts to gradually form and be enclosed in be degraded around thing.2. autophagic vacuole is molded and will be dropped completely
The material of solution is completely isolated in cytoplasm.3. autophagosome forms autophagy lysosome with lysosome fusion.4. autophagy lysosome is final
By the hydrolase dissolving in lysosome, catabolite can recycling in the cell.[Martínez-Borra J,Ló pez-Larrea C.Autophagy and self-defense.Adv Exp Med Biol.2012；738:169-84.]；From
Biting can change and various stimulation generation stress reactions to cell to external environment condition.Cell can occur reduced levels under growth conditions
Autophagy, also referred to as basic autophagy.However, once being stimulated by the external world, such as starvation, anoxic, high temperature, high-cell density or life
Factor withdrawal long etc., the level of cell autophagy will be raised rapidly.Such as in the case where nutriment lacks, cell autophagy can divide
Solving internal non-viable non-apoptotic cell device produces amino acid etc. to synthesize new protein for cell, maintains the survival of cell [1.Piacentini M,D'Eletto M,Falasca L,et al.Transglutaminase 2 at the crossroads between
cell death andsurvival.Adv Enzymol Relat Areas Mol Biol.2011；78:197-246；②Cook KL,Shajahan AN,Clarke R.Autophagy and endocrine resistance in breast
cancer.Expert Rev Anticancer Ther.2011；11(8):1283-94.；③Wirawan E,Vanden Berghe T,Lippens S,et al.Autophagy:for better orfor worse.Cell Res.2012；22
(1):43-61.].However, used as one kind of apoptosis, cell autophagy can be by number of ways either directly or indirectly
Cause cell death.This killing may be by the generation of the mechanism such as inducing cell apoptosis, necrosis, aging, it is also possible to make thin
Born of the same parents directly occur autophagy it is dead [Denton D,Nicolson S,Kumar S.Cell death by autophagy:
facts and apparent artefacts.Cell Death Differ.2012；19(1):87-95.].
Current quantum dot preparation is that traditional preparation process is made, and not only toxicity is larger and negative for tumor cells targeting
Ability, it is difficult to for neoplasm tracing and detection.Present situation based on prior art, present inventor intends providing a kind of targeting lung
The low toxicity quantum dot preparation of cancer.
The content of the invention
The purpose of the present invention is the defect for overcoming prior art to exist, there is provided a kind of lung cancer-targeted low toxicity quantum dot preparation
And preparation method thereof.Quantum dot preparation that more particularly relate to a kind of hypotoxicity, that pulmonary cancer diagnosis can be used for and preparation method thereof.
Its toxicity of quantum dot preparation is less than general quantum dot preparation and the selectively targeted lung cancer of energy.
The present invention is combined with rgd peptide in lung cancer-targeted low toxicity quantum dot preparation is prepared with quantum dot, is assigned and being passed
The ability of system quantum dot targets neoplastic cells, makes to be combined with cell autophagy regulating medicine, weakens its toxicity.Further will amount
Son point is made lung cancer-targeted low toxicity nanometer formulation for lung cancer and other diagnosing tumors.
Specifically, in the present invention, traditional quantum dot is connected with lung cancer targeting molecule, regulate and control with cell autophagy afterwards
Agent constitutes composition or preparation together.
In the present invention, described quantum dot preparation is by one or more lung cancer-targeted quantum dot and one or more cell
Autophagy/reinforcing agent composition.In embodiments of the invention, the quantum dot preparation is by one or more lung cancer-targeted quantum dot and carefully
Born of the same parents' autophagy regulating drug is constituted.
In the present invention, lung cancer-targeted quantum dot is made up of a kind of quantum dot and one or more rgd peptide sequences.
In the present invention, quantum dot includes but is not limited to cadmium telluride quantum dot (CdTe), ZnS quantum dots (ZnS) and selenizing
Cadmium quantum dot (CdSe)；In one embodiment of the present of invention, preferred quantum dot is cadmium telluride (CdTe) quantum dot.
In the present invention, rgd peptide includes but is not limited to C-RGD and Y-RGD, and its sequence is as shown in SEQ No.1；The present invention
One embodiment in, preferred rgd peptide is C-RGD.
Lung cancer-targeted quantum dot of the invention also can constitute composition with autophagy regulating drug, and sequential use is reducing quantum
The toxicity of point.
In the present invention, cell autophagy regulating drug is included but is not limited to：Chloroquine (CQ), 3-MA irrigates graceful penicillin, Bava Lip river
Mycin A-1, ammonium chloride and LY294002；In one embodiment of the present of invention, preferred cell autophagy regulating drug it is optimal be：
Chloroquine, 3-MA and ammonium chloride.
The particle diameter of the prepared quantum dot of the present invention is 12nm or so, and Zeta potential is -32.9mV or so, and maximum excitation wavelength is
259nm, maximum emission wavelength is 656nm.With the due property of quantum dot (as shown in table 1).
The prepared quantum dot preparation of the present invention has carried out the lung cancer targeting comparative experiments with common quantum dot, as a result shows,
Obtained quantum dot can be selectively targeted and be can be incorporated on lung carcinoma cell.
The prepared quantum dot preparation of the present invention has carried out toxicity in vivo evaluation experimental, as a result shows, this quantum dot preparation is in body
Interior relative hypotoxicity, being made preparation with cell autophagy inhibitor can mitigate quantum dot toxicity in vivo.
Further, the obtained quantum dot preparation of the present invention can be used in preparation treatment, diagnosis, the preparation of detection lung cancer；
Can also be used to prepare diagnosis, in detecting and treating the preparation of other tumours；Can be used to prepare the spike of interior tumor cell simultaneously
And location preparation.
Quantum dot preparation of the invention has the following advantages that：
(1) selectively targeted lung carcinoma cell, and fluorescence can be sent.
(2) with the toxicity lower than traditional quantum dot；And
(3) preparation process is simple, applicability is wide, can be used for the production of large-scale.
Brief description of the drawings
Fig. 1 is quantum dot schematic diagram.
Fig. 2 is that this quantum dot preparation compares with the tumour cell imaging of traditional quantum dot.
Fig. 3 and the quantum dot of cell autophagy inhibitor composition and the toxicity in vivo contrast of traditional quantum dot.
Specific embodiment
Embodiment 1 prepares quantum dot preparation
(1) quantum dot is prepared：By appropriate CdCl2, NaHTe and MPA insert in reactor, with the NaBH of pH=9.04It is molten
A certain amount of Na is then added in reactor in 95 DEG C of successive reactions 16 hours under the protection of nitrogen after solution2S, in 60 DEG C
Successive reaction 1.5 hours, the Cd in reactor:Te:S:MPA ratios are 1:0.45:0.0125:4.161, it is stored in 2 DEG C；
(2) lung cancer-targeted quantum dot is prepared：By C-RGD being dissolved in PBS (pH=7.4) and be made 1mg/mL's
RGD small peptides solution (at 4 DEG C dissolve), afterwards in molar ratio 1：1 adds the quantum dot for preparing, and is obtained final product within 4 hours in 4 DEG C of reactions；
(3) quantum dot preparation is prepared：Chloroquine is dissolved in 0.01M PBS (pH=7.4) and to be made 10 μM of chloroquine molten
Liquid, after by prepare the quantum dot with RGD be dissolved in the solution so that heavy metal concentration Cd2+=1 μM；Gained quantum dot system
As shown in figure 1, Fig. 1 shows CdTe quantum in quantum dot solution, table 1 shows that the particle diameter of the quantum dot is for the identification of agent
12nm or so, Zeta potential is -32.9mV or so, and maximum excitation wavelength is 259nm, and maximum emission wavelength is 656nm, with amount
The son due property of point.
The quantum dot of table 1. characterizes statistical form：
The lung cancer targeting comparative experiments of the obtained quantum dot of the present invention of embodiment 2. and common quantum dot
Lung cancer A549 cell and H1975 cells kind are taken in (1 × 10 on laser co-focusing ware5It is individual), treat cell after culture 24h
It is adherent；It is separately added into after this quantum dot is incubated 2 hours jointly with common traditional quantum dot (20nM) and uses PBS washed cells 3 times simultaneously
With the situation of laser co-focusing observation of cell incorporating quantum point, as shown in Fig. 2 A549 cells are being incubated 2h altogether with traditional quantum dot
Afterwards without obvious fluorescence, and with this lung cancer-targeted quantum dot preparation be incubated altogether after 2h cell membrane and it is intracellular have obvious fluorescence,
Prove that this quantum dot is selectively targeted and can be incorporated on lung carcinoma cell.
The toxicity in vivo evaluation test of 3. quantum dot preparations of embodiment
The quantum dot of 0.2nmol and this obtained quantum dot preparation are entered in Mice Body by tail vein injection respectively, respectively
Observation 30 days, each group carries out taking haemanalysis simultaneously its internal organs of dissection and analysis without dead mouse after the conventional treatment to mouse in 30 days,
Result as shown in figure 3, after 30 days common quantum dot liver, kidney and spleen occur in that more serious damage, this obtained quantum
The damage display that point preparation is caused to liver kidney spleen is significantly less than the damage caused by common quantum dot, it was demonstrated that obtained quantum dot system
Agent hypotoxicity relative in vivo, being made new formulation with cell autophagy inhibitor can mitigate quantum dot toxicity in vivo.
Claims (10)
1. a kind of lung cancer-targeted cell quantum dot preparation, it is characterised in that：By one or more lung cancer-targeted quantum dot and cell
Autophagy regulating drug is constituted；Its selectively targeted lung carcinoma cell, and fluorescence and lower than traditional quantum dot toxicity can be sent.
2. the lung cancer-targeted cell quantum dot preparation of claim 1 is pressed, it is characterised in that：Described lung cancer-targeted quantum dot is by one
Plant quantum dot and one or more rgd peptide sequences are constituted.
3. the lung cancer-targeted cell quantum dot preparation as described in claim 1 or 2, it is characterised in that：Described quantum dot is selected from
Cadmium telluride quantum dot (CdTe), ZnS quantum dots (ZnS) and CdSe quantum dots (CdSe).
4. the lung cancer-targeted cell quantum dot preparation as described in claim 1 or 2, it is characterised in that：Described quantum is telluride
Cadmium (CdTe) quantum dot.
5. the lung cancer-targeted cell quantum dot preparation as described in claim 1, it is characterised in that：Described cell autophagy regulating
Thing is selected from chloroquine (CQ), and 3-MA irrigates graceful penicillin, Bava Lip river mycin A-1, ammonium chloride or LY294002.
6. the lung cancer-targeted cell quantum dot preparation as described in claim 1, it is characterised in that：Described cell autophagy regulating
Thing is chloroquine, 3-MA or ammonium chloride.
7. the lung cancer-targeted cell quantum dot preparation as described in claim 2, it is characterised in that：Described rgd peptide is selected from C-
RGD and Y-RGD, its sequence is as shown in SEQ No.1.
8. the lung cancer-targeted cell quantum dot preparation as described in claim 2, it is characterised in that：Described rgd peptide is C-
RGD。
9. a kind of lung cancer-targeted quantum dot by claim 1 constitutes pharmaceutical composition with autophagy regulating drug, it is characterised in that
Described lung cancer-targeted quantum dot is sequential with autophagy regulating drug to be used.
10. the quantum dot preparation described in claim 1 for prepare treatment, diagnosis, detection lung cancer preparation in purposes.
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