Embodiment
Elaborate below in conjunction with the embodiment specific embodiments of the invention.
A kind of water-soluble carbon nanometer tube of the present invention is on carbon nanotube molecule, to pass through chemical bond-linking water receiving soluble polymer polymine, and the mass content of described carbon nanotube and polymine is than being 1:0.085-0.125; Described carbon nanotube is a SWCN.
Described preparation method is:
(1) with carbon nanotube through s.t., the surperficial carbon nanotube that has carboxyl;
(2) surface is had the carbon nanotube and the ammonification reagent react of carboxyl, surperficially have an amino carbon nanotube;
(3) surface is had amino carbon nanotube and Soluol XC 100 reaction, in the presence of hydrionic, Soluol XC 100 constantly carries out grafting on amino, finally form the polymine carbon nanotube, i.e. water-soluble carbon nanometer tube.
The present invention can be provided by following examples in practical implementation.
Embodiment 1
(1) is rare nitric acid of 4mol/L with adding 100mL concentration in the 100mg carbon nanotube, disperses back 110 ℃ of heating, 400r/min stirring and refluxing 2h; Make its sufficient reacting, reaction finishes the back constantly with after the ultrapure water washing and using the filtering with microporous membrane of 0.1 μ m, and adding 100mL concentration is the Hydrogen chloride of 1mol/L; Ultrasonic reaction 30min constantly with the ultrapure water washing, crosses and filters the carbon nanotube filter cake after reaction finishes; With the carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube that the surface has carboxyl;
(2) carbon nanotube and the 2mg NSC 57182 that the 50mg surface are had a carboxyl join in the 20ml quadrol; 120 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Use absolute ethyl alcohol constantly to wash; Cross and filter filter cake, filter cake is vacuumized drying under 40 ℃, obtain the surface and have amino carbon nanotube;
(3) the 40mg surface being had amino carbon nanotube, 0.5ml Soluol XC 100 and 10 μ L volumetric concentrations is that the concentrated hydrochloric acid of 37-38% mixes in the 20ml methylene dichloride; 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Through 20 after-filtration of washed with dichloromethane; Vacuumize drying under 40 ℃, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 2
(1) is rare nitric acid of 4mol/L with adding 100mL concentration in the 100mg carbon nanotube, disperses back 110 ℃ of heating, 400r/min stirring and refluxing 2h; Make its sufficient reacting, reaction finishes the back constantly with after the ultrapure water washing and using the filtering with microporous membrane of 0.1 μ m, and adding 100mL concentration is the Hydrogen chloride of 1mol/L; Ultrasonic reaction 30min constantly with the ultrapure water washing, crosses and filters the carbon nanotube filter cake after reaction finishes; With the carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube that the surface has carboxyl;
(2) carbon nanotube that the 50mg surface is had a carboxyl joins the sulfur oxychloride of 20ml and the mixing solutions of N`-N` N, and the volume ratio of described sulfur oxychloride and N`-N` N is 19:1, and reflux stirs; Fully reaction, after the anhydrous tetrahydro furan washing, suction filtration; Add after excessive quadrol fully stirs; Suction filtration limit, limit gets filter cake 20 times with absolute ethanol washing, and filter cake is vacuumized drying under 40 ℃ of conditions, obtains the surface and has amino carbon nanotube;
(3) the 40mg surface being had amino carbon nanotube, 0.5ml Soluol XC 100 and 10 μ l volumetric concentrations is that the concentrated hydrochloric acid of 37-38% mixes in the 20ml methylene dichloride; 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Through 20 after-filtration of washed with dichloromethane; Vacuumize drying under 40 ℃, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 3
(1) is rare nitric acid of 4mol/L with adding 100mL concentration in the 100mg carbon nanotube, disperses back 110 ℃ of heating, 400r/min stirring and refluxing 2h; Make its sufficient reacting, reaction finishes the back constantly with after the ultrapure water washing and using the filtering with microporous membrane of 0.1 μ m, and adding 100mL concentration is the Hydrogen chloride of 1mol/L; Ultrasonic reaction 30min constantly with the ultrapure water washing, crosses and filters the carbon nanotube filter cake after reaction finishes; With the carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube that the surface has carboxyl;
(2) 1-ethyl-(3-dimethylaminopropyl) the phosphinylidyne diimmonium salt hydrochlorate of 2nM and the N-maloyl imines of 5nM are joined in the 50ml ultrapure water, behind the ultrasonic 15min, add the carbon nanotube that the 50mg surface has carboxyl; Continue ultrasonic 30min; Described mixture pH value remains on below 5, after the ultrasonic end, uses the ultrapure water repetitive scrubbing; Cross and filter filter cake, filter cake is vacuumized drying;
(3) the 40mg surface being had amino carbon nanotube, 0.5ml Soluol XC 100 and 10 μ l volumetric concentrations is that the concentrated hydrochloric acid of 37-38% mixes in the 20ml methylene dichloride; 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Through 20 after-filtration of washed with dichloromethane; Vacuumize drying under 40 ℃, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 4
(1) is rare nitric acid of 4mol/L with adding 100mL concentration in the 100mg carbon nanotube, disperses back 110 ℃ of heating, 400r/min stirring and refluxing 2h; Make its sufficient reacting, reaction finishes the back constantly with after the ultrapure water washing and using the filtering with microporous membrane of 0.1 μ m, and adding 100mL concentration is the Hydrogen chloride of 1mol/L; Ultrasonic reaction 30min constantly with the ultrapure water washing, crosses and filters the carbon nanotube filter cake after reaction finishes; With the carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube that the surface has carboxyl;
(2) carbon nanotube and the 2mg NSC 57182 that the 50mg surface are had a carboxyl join in the 20ml quadrol; 120 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Use absolute ethyl alcohol constantly to wash; Cross and filter filter cake, filter cake is vacuumized drying under 40 ℃, obtain the surface and have amino carbon nanotube;
(3) the 40mg surface being had amino carbon nanotube, 0.5ml Soluol XC 100 and 10 μ l volumetric concentrations is that the concentrated hydrochloric acid of 37-38% mixes in the 20ml methylene dichloride; 70 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction; Through 20 after-filtration of washed with dichloromethane; Vacuumize drying under 40 ℃, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
The particle diameter of described water-soluble carbon nanometer tube is 180-210nm.
Described water-soluble carbon nanometer tube combines with antitumor drug; As the application of drug delivery carrier in the preparation antitumor drug, described antitumor drug is: one or more of the Docetaxel of insoluble anti-tumor medicament, water soluble drug and nucleic acid drug, taxol, Zorubicin, cis-platinum, carboplatin, daunorubicin, few adopted antinucleus thuja acid, siRNA and enzyme drug; Described being combined into: ultrasonic, stir, visit in ultra and the rotary evaporation one or more.
Water-soluble carbon nanometer tube drug delivery carrier associating thermotherapy is as the application of thermotherapy sensitizer in the preparation antitumor drug.
First purpose of the present invention makes up a kind of SWCN-polymine medicament carrier system exactly.
Second purpose of the present invention just provides the preparation method of above-mentioned carrier system.
The 3rd purpose of the present invention just provides above-mentioned SWCN-polyethyleneimine polymers as gene and the application of drug delivery carrier in oncotherapy.
The 4th purpose of the present invention just provides the above-mentioned SWCN-application of the system combined thermotherapy of polymine drug delivery carrier in oncotherapy.
First purpose of the present invention is achieved through following technical scheme:
A kind of SWCN-polyethyleneimine polymers, it is with on the SWCN raw material process basis of purification process, makes the SWCN surface have carboxyl through s.t.; Then with the ammonification reagent react; Behind the SWCN surface connection amino that upward reactive behavior is stronger; React with Soluol XC 100 again; In the presence of hydrionic, Soluol XC 100 constantly carries out grafting on amino, finally forms polymine (PEI) branch-shape polymer (SWNT-PEI) on the SWCN surface.In this SWCN-polyethyleneimine polymers, the mass content of SWNTs and PEI is than being 1:0.085-0.125.
Second purpose of the present invention is achieved through following technical scheme:
The preparation method of the antitumor carrier of a kind of SWNT-PEI, it may further comprise the steps:
1) adds solvent orange 2 A among the SWNTs that purifying is crossed, disperse the post-heating refluxing and stirring to make its sufficient reacting.After finishing, reaction constantly use solution B to wash and filter.To pass through among the SWNTs of above-mentioned processing and add solvent C, ultrasonic reaction, the reaction back that finishes is constantly used the solution B washing and is filtered, and with the SWNTs filtration cakes torrefaction, obtains the SWNTs (SWNT-COOH) that the surface has carboxyl.
2) SWNT-COOH and condensing agent D are added in the ammonification reagent E, reflux stirs fully reaction.With an organic solvent F constantly washs and the filtering reaction product, and filter cake is vacuumized drying, obtains the surface and has amino SWNTs (SWNT-NH
2).
Perhaps SWNT-COOH is joined among the mixed solution G, reflux stirs fully reaction.Use solvent H to wash repeatedly and suction filtration, add in the ammonification reagent E and fully stir, reaction completion suction filtration limit, back vacuumizes drying with organic solvent F thorough washing with filter cake.
Perhaps mixed liquor I is joined in the ultrapure water, ultrasonic back adds SWNT-COOH in mixed solution, continues ultrasonicly, and mixture pH value remains on below 5, prevents hydrolysis.After the ultrasonic end,, filter cake is vacuumized drying with solution B repetitive scrubbing and filtration.
3) with above-mentioned SWNT-NH
2, Soluol XC 100 and concentrated hydrochloric acid mix in organic solvent J, reflux stirs fully reaction, after organic solvent J washing and filtering, vacuum-drying obtains the SWNTs polyethylenimine derivates (SWNT-PEI) that surface grafting forms polymine.
SWNTs is 100mg in the above-mentioned steps 1; Solvent orange 2 A, B are 100ml; The reflux agitation condition is 400r/min, and 90-110 ℃, the time is 2-3h; Ultrasound condition is 80-100KHz, and 30-50 ℃, the time is 0.5-1h; The washing and filtering condition is that last filtrating pH value is neutrality, and the filter membrane aperture is 0.1 μ m.
Solvent orange 2 A is rare nitric acid in the above-mentioned steps 1; Solvent B is a ultrapure water in the above-mentioned steps 1; Solvent C is a Hydrogen chloride in the above-mentioned steps 1.
SWNT-COOH is 50mg in the above-mentioned steps 2; Condensing agent D is 2g; The ammonification reagent E is 20ml; Condition of heating and stirring is 400r/min, and 110-120 ℃, the time is 24-48h; Mixing solutions G is 20ml; EDC is 2nm among the mixture I, and NHS is 5nm; The washing and filtering condition is that organic solvent F or organic solvent H wash 15-20 time, and the filter membrane aperture is 0.1 μ m; Vacuum drying condition is at 40-60 ℃ of vacuum-drying 24-48h.
It is NSC 57182 (DCC) that condensing agent D is arranged in the above-mentioned steps 2.
The ammonification reagent E is a quadrol, 1 in the above-mentioned steps 2,3-tn, 1, a kind of in the 6-hexanediamine.
Organic solvent F is an absolute ethyl alcohol in the above-mentioned steps 2.
Mixed solution G is sulfur oxychloride (SOCl in the above-mentioned steps 2
2) with the mixing solutions of N`-N` N (DMF).
Organic solvent H is anhydrous tetrahydro furan (THF) in the above-mentioned steps 2.
Mixed liquor I is 1-ethyl-(3-dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate (EDC) and N-maloyl imines (NHS) in the above-mentioned steps 2.
SWNT-NH in the above-mentioned steps 3
2Be 40mg; Soluol XC 100 is 0.5ml; Concentrated hydrochloric acid is 10-20 μ l; Organic solvent J is 20ml; The reflux agitation condition is 400r/min, and 30-40 ℃ or 60-70 ℃, the time is 24-72h; The washing and filtering condition is organic solvent J washing 15-20 time, and the filter membrane aperture is 0.1 μ m; Vacuum drying condition is at 40-60 ℃ of vacuum-drying 24-48h.
Organic solvent J is Ethylene Dichloride or methylene dichloride in the above-mentioned steps 3.
The 3rd purpose of the present invention is achieved through following technical scheme:
SWCN-polymine is divided into following step as the application of pharmaceutical carrier in oncotherapy:
1) SWCN-polyethyleneimine polymers that makes and antitumor drug A pass-through mode B are combined.
2) SWCN-polyethyleneimine polymers of drug loading is carried out the evaluation of antitumor cell C and intravital antitumor D.
Antitumor drug A in the above-mentioned steps 1 is: insoluble anti-tumor medicament, water soluble drug and nucleic acid drug, as: one or more in Docetaxel, taxol, Zorubicin, cis-platinum, daunorubicin, few adopted antinucleus thuja acid, siRNA and the enzyme drug.
Mode B in the above-mentioned steps 1 is: ultrasonic, stirring, vortex, spy is ultra and rotary evaporation in one or more.
Tumour cell C in the above-mentioned steps 2 is: organ surface or the inner various solid tumors that occur, lung cancer, nasopharyngeal carcinoma, esophagus cancer, cancer of the stomach, liver cancer, large bowel cancer; Mammary cancer, ovarian cancer, bladder cancer, white blood disease, carcinoma of the pancreas, cervical cancer, laryngocarcinoma; Thyroid carcinoma, tongue cancer, brain tumor (intracranial tumors), intestinal tumor, carcinoma of gallbladder, cholangiocarcinoma; Kidney, prostate cancer, penile cancer, tumor of testis, carcinoma of endometrium, choriocarcinoma; The vagina malignant tumour, vulva malignant tumour, Hodgkin, non-Hodgkin lymphoma, skin carcinoma, a kind of in the malignant melanoma.
Tumour D in the above-mentioned steps 2 is: organ surface or the inner various solid tumors that occur, lung cancer, nasopharyngeal carcinoma, esophagus cancer, cancer of the stomach, liver cancer, large bowel cancer; Mammary cancer, ovarian cancer, bladder cancer, white blood disease, carcinoma of the pancreas, cervical cancer, laryngocarcinoma; Thyroid carcinoma, tongue cancer, brain tumor (intracranial tumors), intestinal tumor, carcinoma of gallbladder, cholangiocarcinoma; Kidney, prostate cancer, penile cancer, tumor of testis, carcinoma of endometrium, choriocarcinoma; The vagina malignant tumour, vulva malignant tumour, Hodgkin, non-Hodgkin lymphoma, skin carcinoma, a kind of in the malignant melanoma.
The 4th of the present invention is achieved through following technical scheme:
Wall carbon nano tube-the application of the system combined thermotherapy of polymine drug delivery carrier in oncotherapy is divided into two portions in external and the body:
1) SWCN that makes-polymine medicament carrier system is dissolved in the solution A, joins among the cancer cells B and cultivate, shine 1min with light source C behind the 6h after the administration, continue to cultivate 24 hours, measure the survival rate of cancer cells B.
2) SWCN that makes-polymine medicament carrier system is dissolved in processes solution among the D, intravenous injection is in tumor-bearing mice E body, and with light source C irradiation tumor locus 1min, the gross tumor volume of measuring tumor-bearing mice E is big or small after each administration.
Solution A in the above-mentioned steps 1 is: ultrapure water, 5% glucose solution, saline water or damping fluid (RNase free).
Cancer cells B in the above-mentioned steps 1 is: organ surface or the inner various solid tumors that occur, lung cancer, nasopharyngeal carcinoma, esophagus cancer, cancer of the stomach, liver cancer, large bowel cancer; Mammary cancer, ovarian cancer, bladder cancer, white blood disease, carcinoma of the pancreas, cervical cancer, laryngocarcinoma; Thyroid carcinoma, tongue cancer, brain tumor (intracranial tumors), intestinal tumor, carcinoma of gallbladder, cholangiocarcinoma; Kidney, prostate cancer, penile cancer, tumor of testis, carcinoma of endometrium, choriocarcinoma; The vagina malignant tumour, vulva malignant tumour, Hodgkin, non-Hodgkin lymphoma, skin carcinoma, a kind of in the malignant melanoma.
Light source C in the above-mentioned steps 1 is: a kind of in the near-infrared laser of 808nm or 980nm wavelength.
Solution D in the above-mentioned steps 2 is: ultrapure water, 5% glucose solution, saline water or damping fluid (RNase free).
Tumor-bearing mice E in the above-mentioned steps 2 is: organ surface or the inner various solid tumors that occur, lung cancer, nasopharyngeal carcinoma, esophagus cancer, cancer of the stomach, liver cancer, large bowel cancer; Mammary cancer, ovarian cancer, bladder cancer, white blood disease, carcinoma of the pancreas, cervical cancer, laryngocarcinoma; Thyroid carcinoma, tongue cancer, brain tumor (intracranial tumors), intestinal tumor, carcinoma of gallbladder, cholangiocarcinoma; Kidney, prostate cancer, penile cancer, tumor of testis, carcinoma of endometrium, choriocarcinoma; The vagina malignant tumour, vulva malignant tumour, Hodgkin, non-Hodgkin lymphoma, skin carcinoma, a kind of in the malignant melanoma.
Light source C in the above-mentioned steps 2 is: a kind of in the near-infrared laser of 808nm or 980nm wavelength.
SWCN among the present invention-polymine drug delivery carrier system can more be distributed in the tumor tissues; Compare with healthy tissues; It can secular high density be retained in the tumor tissues; When adopting suitable means to use near-infrared light source to shine, can in tumor tissues, produce more anti-tumor activity like this, and the medicine of its loading is improved in tumor locus concentration, but this drug delivery system also can be distributed in the normal histoorgan; For fear of healthy tissues is produced damage; Can improve through some means, such as: can in SWCN-polymine drug delivery carrier system, load some and have the target head of target character, also can use means mediations such as antibody; Can use clinical means such as next drug-loading system arrival target tissue, the modes such as focusing illuminating area of directly carrying of the mode of endoscope.
The present invention through test of many times, has all obtained good test-results as the medicine of pharmaceutical carrier preparation treatment tumour, and the correlation test data are following:
Experiment 1
The present invention is as the application of drug delivery carrier in anti-tumor medicine.
Get water-soluble carbon nanometer tube 4mg of the present invention, add the ultrapure water of 2ml, the ultrasonic 2h of 100KHz, the centrifugal 15min of 4000rpm, centrifugal 3 times.Add the 2mg Zorubicin, continue ultrasonic 2h, use ultrafiltration system to filter and remove the Zorubicin that does not combine, the part on the filter membrane is resuspended, promptly get SWCN-polymine/Zorubicin (SWNT-PEI/DOX) carrier system.Ultraviolet spectrophotometer is measured the content that water-soluble carbon nanometer tube of the present invention is the Zorubicin sealed of carrier, and drug loading is 1.9 mg/ml.
Verified, water-soluble carbon nanometer tube of the present invention can effectively carry Zorubicin, and Zorubicin has been produced certain slow releasing function, and the carrier that can be used as Zorubicin uses.
Experiment 2
Water-soluble carbon nanometer tube of the present invention is as the application of genomic medicine transport vehicle in anti-tumor medicine.
Get water-soluble carbon nanometer tube 4mg of the present invention, add 5% glucose solution (RNase free) of 2ml, the ultrasonic 2h of 100KHz, the centrifugal 15min of 4000rpm, centrifugal 3 times.Add siRNA, make the mass ratio of SWNTs and siRNA reach 5:1, promptly be built into water-soluble mono wall carbon nano tube-polymine/siRNA (SWNT/siRNA) carrier system.
Verified, water-soluble carbon nanometer tube of the present invention can active adsorption siRNA, and it is produced protection to a certain degree, and the carrier that can be used as siRNA uses.
Experiment 3
The anti tumor activity in vitro experiment of water-soluble mono wall carbon nano tube-polymine/siRNA (SWNT-PEI/siRNA) drug delivery system.
The anti tumor activity in vitro of the water-soluble SWNT-PEI/siRNA drug delivery system in the experiment 2 is used as cancer cells to be investigated with PC-3 Human Prostate Cancer Cells (being provided by the Shanghai cell bank).The PC-3 cell cultures is being contained foetal calf serum (FBS) 10%, and in the RPMI1640 substratum of mycillin mixed solution 1%, the incubator condition is 37 ℃, 5% CO
2, went down to posterity once in per 2~3 days.Collect the logarithmic phase cell, the adjustment concentration of cell suspension, the every hole of 96 orifice plates adds 200 μ l, and bed board makes cell to be measured transfer density to 5 * 10
3Individual/hole (marginal pore is filled with aseptic PBS).Place 5% CO
2, hatch 24 h for 37 ℃, to cell degree of converging be 50%, the SWNT/siRNA carrier system in the experiment 2 of adding (siRNA concentration is 150nM), not adding the SWNT/siRNA of experiment in 2 is control group, it is 4~6 that multiple hole is set.Laser group is placed on 1min under 808nm near-infrared laser (1.2-1.5W) condition, and laser radiation places CO with cell plate after finishing
2Hatch 24h, 48h and 72h in the incubator, for not illumination group, then directly cell plate are placed CO
2Hatch 24h, 48h and 72h in the incubator, stop cultivating, sucking-off pastille substratum, every hole is washed 2 times with 150 μ l PBS, adds 10% TCA, the 200 μ l of precooling, places 1h for 4 ℃.Outwell stationary liquid, every hole is washed 5 times with deionized water, dries dry air.Every hole adds the SRB solution of 100 μ l, leaves standstill to place 10min, does not wash 5 times dry air with 1% acetic acid with protein bound SRB.Bonded SRB is with the non-buffering of 150 μ l 10mmol/L Tris alkali dissolution.Measure the OD value in every hole at the 515nm place.The calculation formula of inhibiting rate: inhibiting rate=1-experimental group OD value/control group OD value, wherein experimental group and control group are the value after the deduction blank group.
Verified, water-soluble carbon nanometer tube of the present invention can drug loading during as pharmaceutical carrier to get into tumour cell inner, better given play to the curative effect of antitumor drug, and after combining laserthermia, more the propagation of obvious suppression tumour cell.
Experiment 4
The anti-tumor in vivo activity experiment of water-soluble mono wall carbon nano tube-polymine/siRNA (SWNT-PEI/siRNA) drug delivery system in the experiment 2.
The anti-tumor in vivo of the SWNT-PEI/siRNA drug delivery system in the experiment 2 is active, gets PC-3 human prostate oncocyte, and it is 2 * 10 that the counting back is diluted to concentration with injection saline water
7The cell suspension of individual/ml, and subcutaneous vaccination and BALB/c nude mice (male, 4~6W, 18~22g) right fore tops.After the mouse inoculation tumour 7 days, get wherein 24 gross tumor volume>=60mm
3Nude mice is divided into 4 groups at random, 6 every group.The concrete grouping as follows: (1) control group (NS group): saline water; (2) SWNT-PEI group; (3) SWNT-PEI/siRNA group; (4) SWNT-PEI/siRNA laser therapy group.The dosage of siRNA is 1mg/kg.4 groups of modes that all adopt intravenously administrable, wherein laser radiation is taken the light source that uses of group and is the green picture light source of 808nm, and power is 1.2-1.5W, laser radiation tumor locus behind the administration 3h, the once irradiating time is 1min.Every 3d is administered once, and administration is 6 times altogether.Observe the mouse animation every day in the whole experiment, and every 2d claims its body weight and uses the major diameter (A) and minor axis (B) of vernier caliper measurement murine sarcoma, calculates gross tumor volume.
When the water-soluble mono wall carbon nano tube-polymine of administration experiment 2/siRNA carrier system, the increase of the gross tumor volume of nude mice is compared with blank control group and has been obtained obvious suppression.After merging laser radiation, the increase of nude mice gross tumor volume has obtained obvious suppression more.
When doing above-mentioned experiment, also adopt other near infrared sources and antitumor drug to do similar experiment, all obtained identical and similar result, the present invention's science of dividing into groups, method is reliable and stable, and other experimental results are enumerated no longer one by one.
The invention provides a kind of water-soluble mono wall carbon nano tube and preparation method thereof, with and as the application of drug delivery carrier and associating near-infrared laser thermotherapy.Water-soluble mono wall carbon nano tube of the present invention does not destroy the structural performance of carbon nanotube itself, and test result shows, the SWCN soluble derivative among the present invention; Water dispersible is strong, and very low to the toxicity of organism, physics and chemicalstability are good; Quality is good; The condition of preparation satisfies easily, and raw material sources are abundant, and cost is low.
Water-soluble mono wall carbon nano tube provided by the invention can be used as a kind of good antitumor drug or the carrier of gene, and minimum toxicity is arranged itself, and stronger is water-soluble, good biocompatibility, and specific surface area is big, the unreactiveness advantages of higher.Test result shows; Water-soluble mono wall carbon nano tube provided by the invention is during as the carrier of antitumor drug or gene, and particle diameter is even, can improve the water-soluble of water-insoluble antitumor drug; Can play certain slow releasing function, but also can more arrive in the tumor tissues.
Water-soluble mono wall carbon nano-tube pipe jointing near-infrared laser thermotherapy provided by the invention can also have been given play to more outstanding anti-tumor activity, test shows no matter be external or body in can the good restraining tumour cell under the situation of thermotherapy and the generation and the development of related tissue.Expection can be used to treat a kind of good thermotherapy sensitizer of tumour, can also be that one on the medication preparation innovated greatly as the transport vehicle of chemicals, protein, nucleic acid.
The present invention compared with prior art has following outstanding useful technique effect:
1) the water-soluble mono wall carbon nano tube among the present invention does not have destruction to the characteristic of carbon nanotube itself, and water dispersible is strong, and very low to the toxicity of organism, physics and chemicalstability are good, and quality is good, and the condition of preparation satisfies easily, and raw material sources are abundant, and cost is low.
2) water-soluble mono wall carbon nano tube provided by the invention can be used as a kind of carrier of good antitumor drug, and minimum toxicity is arranged, and stronger is water-soluble, good biocompatibility, and specific surface area is big, and unreactiveness is high, has slow-releasing.
3) water-soluble mono wall carbon nano tube provided by the invention combines thermotherapy can also give play to more outstanding anti-tumor activity; Can bring into play antineoplastic activity during the near-infrared laser irradiation; Then spinoff is very little during not illumination, can come optionally killing tumor cells tissue and cell according to the means such as focusing of laser.