Embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is elaborated.
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 described carbon nanotube and the mass content of polymine are than being 1:0.085-0.125; Described carbon nanotube is Single Walled Carbon Nanotube.
Described preparation method is:
(1) by carbon nanotube by acid treatment, obtain the surperficial carbon nanotube with carboxyl;
(2) carbon nanotube and the ammonification reagent react with carboxyl by surface, obtains surperficial with amino carbon nanotube;
(3) surface is reacted with aziridine with amino carbon nanotube, under hydrionic existence, aziridine constantly carries out grafting on amino, finally forms polymine carbon nanotube, i.e. water-soluble carbon nanometer tube.
The present invention can be provided by following examples in concrete enforcement.
Embodiment 1
(1) be rare nitric acid of 4mol/L by adding 100mL concentration in 100mg carbon nanotube, disperse rear 110 ℃ of heating, 400r/min stirring and refluxing 2h, makes its sufficient reacting, constantly washs and uses after the filtering with microporous membrane of 0.1 μ m with ultrapure water after completion of the reaction, adding 100mL concentration is the dilute hydrochloric acid of 1mol/L, ultrasonic reaction 30min, constantly with ultrapure water washing, filters to obtain carbon nanotube filter cake after completion of the reaction, by carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube of surface with carboxyl;
(2) 50mg surface is joined in 20ml quadrol with carbon nanotube and the 2mg dicyclohexylcarbodiimide of carboxyl, 120 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, use dehydrated alcohol constantly to wash, filter to obtain filter cake, filter cake is vacuumized at 40 ℃ dry, obtain surface with amino carbon nanotube;
(3) concentrated hydrochloric acid that is 37-38% by 40mg surface with amino carbon nanotube, 0.5ml aziridine and 10 μ L volumetric concentrations mixes in 20ml methylene dichloride, 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, after washed with dichloromethane 20 times, filter, at 40 ℃, vacuumize dryly, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 2
(1) be rare nitric acid of 4mol/L by adding 100mL concentration in 100mg carbon nanotube, disperse rear 110 ℃ of heating, 400r/min stirring and refluxing 2h, makes its sufficient reacting, constantly washs and uses after the filtering with microporous membrane of 0.1 μ m with ultrapure water after completion of the reaction, adding 100mL concentration is the dilute hydrochloric acid of 1mol/L, ultrasonic reaction 30min, constantly with ultrapure water washing, filters to obtain carbon nanotube filter cake after completion of the reaction, by carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube of surface with carboxyl;
(2) 50mg surface is joined to the sulfur oxychloride of 20ml and the mixing solutions of N`-N` dimethyl formamide with the carbon nanotube of carboxyl, the volume ratio of described sulfur oxychloride and N`-N` dimethyl formamide is 19:1, reflux stirs, fully reaction, with after anhydrous tetrahydro furan washing, suction filtration, after adding excessive quadrol fully to stir, suction filtration limit, limit with absolute ethanol washing 20 times filter cake, filter cake is vacuumized under 40 ℃ of conditions dry, obtain surface with amino carbon nanotube;
(3) concentrated hydrochloric acid that is 37-38% by 40mg surface with amino carbon nanotube, 0.5ml aziridine and 10 μ l volumetric concentrations mixes in 20ml methylene dichloride, 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, after washed with dichloromethane 20 times, filter, at 40 ℃, vacuumize dryly, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 3
(1) be rare nitric acid of 4mol/L by adding 100mL concentration in 100mg carbon nanotube, disperse rear 110 ℃ of heating, 400r/min stirring and refluxing 2h, makes its sufficient reacting, constantly washs and uses after the filtering with microporous membrane of 0.1 μ m with ultrapure water after completion of the reaction, adding 100mL concentration is the dilute hydrochloric acid of 1mol/L, ultrasonic reaction 30min, constantly with ultrapure water washing, filters to obtain carbon nanotube filter cake after completion of the reaction, by carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube of surface with carboxyl;
(2) the N-maloyl imines of the 1-ethyl of 2nM-(3-dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate and 5nM is joined in 50ml ultrapure water, after ultrasonic 15min, add the carbon nanotube of 50mg surface with carboxyl, continue ultrasonic 30min, described mixture pH value remains on below 5, after ultrasonic end, uses ultrapure water repetitive scrubbing, filter to obtain filter cake, filter cake is vacuumized dry;
(3) concentrated hydrochloric acid that is 37-38% by 40mg surface with amino carbon nanotube, 0.5ml aziridine and 10 μ l volumetric concentrations mixes in 20ml methylene dichloride, 40 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, after washed with dichloromethane 20 times, filter, at 40 ℃, vacuumize dryly, obtain polymine amine carbon nanotube, i.e. water-soluble carbon nanometer tube.
Embodiment 4
(1) be rare nitric acid of 4mol/L by adding 100mL concentration in 100mg carbon nanotube, disperse rear 110 ℃ of heating, 400r/min stirring and refluxing 2h, makes its sufficient reacting, constantly washs and uses after the filtering with microporous membrane of 0.1 μ m with ultrapure water after completion of the reaction, adding 100mL concentration is the dilute hydrochloric acid of 1mol/L, ultrasonic reaction 30min, constantly with ultrapure water washing, filters to obtain carbon nanotube filter cake after completion of the reaction, by carbon nanotube filtration cakes torrefaction, obtain the carbon nanotube of surface with carboxyl;
(2) 50mg surface is joined in 20ml quadrol with carbon nanotube and the 2mg dicyclohexylcarbodiimide of carboxyl, 120 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, use dehydrated alcohol constantly to wash, filter to obtain filter cake, filter cake is vacuumized at 40 ℃ dry, obtain surface with amino carbon nanotube;
(3) concentrated hydrochloric acid that is 37-38% by 40mg surface with amino carbon nanotube, 0.5ml aziridine and 10 μ l volumetric concentrations mixes in 20ml methylene dichloride, 70 ℃ of heating, 400r/min stirring and refluxing 48h, fully reaction, after washed with dichloromethane 20 times, filter, at 40 ℃, vacuumize dryly, 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 is combined with antitumor drug, as drug delivery carrier, in the application of preparing in antitumor drug, described antitumor drug is: one or more of Docetaxel, taxol, Zorubicin, cis-platinum, carboplatin, daunorubicin, few adopted antinucleus thuja acid, siRNA and the enzyme drug of insoluble anti-tumor medicament, water soluble drug and nucleic acid drug; Described is combined into: ultrasonic, stir, visit one or more in super and rotary evaporation.
Water-soluble carbon nanometer tube drug delivery carrier associating thermotherapy as thermotherapy sensitizer in the application of preparing in antitumor drug.
First object of the present invention builds a kind of Single Walled Carbon Nanotube-polymine medicament carrier system exactly.
Second object of the present invention is just to provide the preparation method of above-mentioned carrier system.
The 3rd object of the present invention is just to provide the application in oncotherapy as gene and drug delivery carrier of above-mentioned Single Walled Carbon Nanotube-polyethyleneimine polymers.
The 4th object of the present invention is just to provide the application of the system combined thermotherapy of above-mentioned Single Walled Carbon Nanotube-polymine drug delivery carrier in oncotherapy.
First object of the present invention is achieved by the following technical programs:
A kind of Single Walled Carbon Nanotube-polyethyleneimine polymers, it is by the Single Walled Carbon Nanotube raw material process basis of purification process, makes Single Walled Carbon Nanotube surface with carboxyl by acid treatment; Then with ammonification reagent react, Single Walled Carbon Nanotube surface is connected after the amino that upper reactive behavior is stronger, react with aziridine again, under hydrionic existence, aziridine constantly carries out grafting on amino, finally forms polymine (PEI) branch-shape polymer (SWNT-PEI) on Single Walled Carbon Nanotube surface.In this Single Walled Carbon Nanotube-polyethyleneimine polymers, the mass content of SWNTs and PEI is than being 1:0.085-0.125.
Second object of the present invention is achieved by the following technical programs:
A preparation method for the antitumor carrier of SWNT-PEI, it comprises the following steps:
1) in SWNTs purifying being crossed, add solvent orange 2 A, disperse post-heating return stirring to make its sufficient reacting.Constantly use after completion of the reaction solution B to wash and filter.To add solvent C through in the SWNTs of above-mentioned processing, ultrasonic reaction, constantly uses solution B to wash and filter after completion of the reaction, by SWNTs filtration cakes torrefaction, obtains the SWNTs(SWNT-COOH of surface with carboxyl).
2) SWNT-COOH and condensing agent D are added in ammonification reagent E, reflux stirs fully reaction.With an organic solvent F constantly washs and filters reaction product, filter cake is vacuumized dry, obtain surface with amino SWNTs(SWNT-NH
2).
Or SWNT-COOH is joined in mixed solution G, and reflux stirs fully reaction.Use solvent H to wash repeatedly and suction filtration, add in ammonification reagent E and fully stir, reacted suction filtration limit, back organic solvent F and fully washed, filter cake is vacuumized dry.
Or mixed liquor I is joined in ultrapure water, add SWNT-COOH in mixed solution after ultrasonic, continue ultrasonicly, mixture pH value remains on below 5, precaution of hydrolysis.After ultrasonic end, with solution B repetitive scrubbing filtration, filter cake is vacuumized dry.
3) by above-mentioned SWNT-NH
2, aziridine and concentrated hydrochloric acid mix in organic solvent J, reflux stirs fully reaction, after organic solvent J wash and filters, vacuum-drying, obtains the SWNTs polyethylenimine derivates (SWNT-PEI) of surface grafting formation polymine.
In above-mentioned steps 1, SWNTs is 100mg; Solvent orange 2 A, B are 100ml; Reflux agitation condition is 400r/min, 90-110 ℃, and the time is 2-3h; Ultrasound condition is 80-100KHz, 30-50 ℃, and the time is 0.5-1h; Washing and filtering condition is that last filtrate pH value is neutrality, and filter membrane aperture is 0.1 μ m.
In above-mentioned steps 1, solvent orange 2 A is rare nitric acid; In above-mentioned steps 1, solvent B is ultrapure water; In above-mentioned steps 1, solvent C is dilute hydrochloric acid.
In above-mentioned steps 2, SWNT-COOH is 50mg; Condensing agent D is 2g; Ammonification reagent E is 20ml; Condition of heating and stirring is 400r/min, 110-120 ℃, and the time is 24-48h; Mixing solutions G is 20ml; In mixture I, EDC is 2nm, and NHS is 5nm; Washing and filtering condition is that organic solvent F or organic solvent H wash 15-20 time, and filter membrane aperture is 0.1 μ m; Vacuum drying condition is at 40-60 ℃ of vacuum-drying 24-48h.
In above-mentioned steps 2, having condensing agent D is dicyclohexylcarbodiimide (DCC).
In above-mentioned steps 2, ammonification reagent E is quadrol, 1,3-propylene diamine, 1, the one in 6-hexanediamine.
In above-mentioned steps 2, organic solvent F is dehydrated alcohol.
In above-mentioned steps 2, mixed solution G is sulfur oxychloride (SOCl
2) with the mixing solutions of N`-N` dimethyl formamide (DMF).
In above-mentioned steps 2, organic solvent H is anhydrous tetrahydro furan (THF).
In above-mentioned steps 2, mixed liquor I is 1-ethyl-(3-dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate (EDC) and N-maloyl imines (NHS).
SWNT-NH in above-mentioned steps 3
2for 40mg; Aziridine is 0.5ml; Concentrated hydrochloric acid is 10-20 μ l; Organic solvent J is 20ml; Reflux agitation condition is 400r/min, 30-40 ℃ or 60-70 ℃, and the time is 24-72h; Washing and filtering condition is organic solvent J washing 15-20 time, and filter membrane aperture is 0.1 μ m; Vacuum drying condition is at 40-60 ℃ of vacuum-drying 24-48h.
In above-mentioned steps 3, organic solvent J is Ethylene Dichloride or methylene dichloride.
The 3rd object of the present invention is achieved by the following technical programs:
Single Walled Carbon Nanotube-polymine is the application in oncotherapy as pharmaceutical carrier, is divided into following step:
1) Single Walled Carbon Nanotube-polyethyleneimine polymers making and antitumor drug A pass-through mode B are carried out to combination.
2) Single Walled Carbon Nanotube-polyethyleneimine polymers of drug loading is carried out to the evaluation of the antitumor D in antitumor cell C and body.
Antitumor drug A in 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 enzyme drug.
Mode B in above-mentioned steps 1 is: one or more in the super and rotary evaporation of ultrasonic, stirring, vortex, spy.
Tumour cell C in 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, leukemia, 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, For Primary Vaginal Carcinoma, Vulvar, Hodgkin's disease, non-Hodgkin lymphoma, skin carcinoma, one in malignant melanoma.
Tumour D in 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, leukemia, 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, For Primary Vaginal Carcinoma, Vulvar, Hodgkin's disease, non-Hodgkin lymphoma, skin carcinoma, one in malignant melanoma.
The 4th of the present invention is achieved by the following technical programs:
The application of the system combined thermotherapy of wall carbon nano tube-polymine drug delivery carrier in oncotherapy is divided in vitro and in vivo two portions:
1) Single Walled Carbon Nanotube-polymine medicament carrier system making is dissolved in solution A, joins in cancer cells B and cultivate, after administration, after 6h, irradiate 1min with light source C, continue to cultivate 24 hours, measure the survival rate of cancer cells B.
2) Single Walled Carbon Nanotube-polymine medicament carrier system making is dissolved in D and makes solution, intravenous injection, in tumor-bearing mice E body, is irradiated tumor locus 1min with light source C after each administration, measures the gross tumor volume size of tumor-bearing mice E.
Solution A in above-mentioned steps 1 is: ultrapure water, 5% glucose solution, physiological saline or damping fluid (RNase free).
Cancer cells B in 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, leukemia, 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, For Primary Vaginal Carcinoma, Vulvar, Hodgkin's disease, non-Hodgkin lymphoma, skin carcinoma, one in malignant melanoma.
Light source C in above-mentioned steps 1 is: the one in the near-infrared laser of 808nm or 980nm wavelength.
Solution D in above-mentioned steps 2 is: ultrapure water, 5% glucose solution, physiological saline or damping fluid (RNase free).
Tumor-bearing mice E in 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, leukemia, 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, For Primary Vaginal Carcinoma, Vulvar, Hodgkin's disease, non-Hodgkin lymphoma, skin carcinoma, one in malignant melanoma.
Light source C in above-mentioned steps 2 is: the one in the near-infrared laser of 808nm or 980nm wavelength.
Single Walled Carbon Nanotube-polymine drug delivery carrier system in the present invention can more be distributed in tumor tissues, compared with healthy tissues, it can be long-term being retained in tumor tissues of high density, in the time adopting suitable means to use near-infrared light source to irradiate, can in tumor tissues, produce more anti-tumor activity like this, and can make the medicine of its loading improve in tumor locus concentration, but this drug delivery system also can be distributed in normal histoorgan, produce damage for fear of normal tissue, can be improved by some means, such as: the target head that can load some in Single Walled Carbon Nanotube-polymine drug delivery carrier system and have target character, also can use the means mediations such as antibody, can be with clinical means such as the mode of endoscope directly carries drug-loading system to arrive target tissue, focus on the modes such as illuminating area.
The present invention, as the medicine of pharmaceutical carrier preparation treatment tumour, through test of many times, has all obtained good test-results, and correlation test data are as follows:
Experiment 1
The present invention is the application in anti-tumor medicine as drug delivery carrier.
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 2mg Zorubicin, continue ultrasonic 2h, use ultrafiltration system to filter and remove not in conjunction with upper Zorubicin, by resuspended the part on filter membrane, obtain Single Walled Carbon Nanotube-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 to 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 the application in anti-tumor medicine as genomic medicine transport vehicle.
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, 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 to protection to a certain degree, and the carrier that can be used as siRNA uses.
Experiment 3
Water-soluble mono wall carbon nano tube-polymine/siRNA(SWNT-PEI/siRNA) the anti tumor activity in vitro experiment of drug delivery system.
The anti tumor activity in vitro of the water-soluble SWNT-PEI/siRNA drug delivery system in experiment 2, is used as cancer cells to be investigated by PC-3 Human Prostate Cancer Cells (being provided by Shanghai cell bank).PC-3 cell cultures is being contained to foetal calf serum (FBS) 10%, and in the RPMI1640 substratum of mycillin mixed solution 1%, incubator condition is 37 ℃, 5% CO
2, within every 2~3 days, go down to posterity once.Collect logarithmic phase cell, adjust concentration of cell suspension, the 96 every holes of orifice plate add 200 μ l, and bed board makes cell to be measured adjust density to 5 × 10
3individual/hole (marginal pore is filled with aseptic PBS).Be placed in 5% CO
2, hatch 24 h for 37 ℃, to cell degree of converging be 50%, the SWNT/siRNA carrier system (siRNA concentration is 150nM) in the experiment 2 adding, 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, after laser radiation finishes, cell plate is placed in to CO
2in incubator, hatch 24h, 48h and 72h, for light group not, directly cell plate are placed in to CO
2in incubator, hatch 24h, 48h and 72h, stop cultivating, sucking-off pastille substratum, every hole is washed 2 times with 150 μ l PBS, adds 10% TCA 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 and places 10min, does not wash 5 times dry air with 1% acetic acid with protein bound SRB.In conjunction with the non-buffering of 150 μ l 10mmol/L Tris alkali dissolution for SRB.Measure the OD value in every hole at 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 deduction blank group.
Verified, water-soluble carbon nanometer tube of the present invention can drug loading enter tumour cell inside during as pharmaceutical carrier, has better given play to the curative effect of antitumor drug, and in conjunction with after laserthermia, the more obviously propagation of inhibition tumor cell.
Experiment 4
Water-soluble mono wall carbon nano tube-polymine/the siRNA(SWNT-PEI/siRNA of experiment in 2) the anti-tumor in vivo activity experiment of drug delivery system.
The anti-tumor in vivo activity of the SWNT-PEI/siRNA drug delivery system in experiment 2, gets PC-3 human prostate oncocyte, after counting, becomes concentration as 2 × 10 take injection normal saline dilution
7the cell suspension of individual/ml, subcutaneous vaccination and BALB/c nude mice (male, 4~6W, 18~22g) right fore top.After mouse inoculation tumour 7 days, get wherein 24 gross tumor volume>=60mm
3nude mice, is divided into 4 groups at random, 6 every group.Specifically be grouped as follows: (1) control group (NS group): physiological saline; (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 all adopt the mode of intravenously administrable, wherein laser radiation take group use light source be the green picture light source of 808nm, power is 1.2-1.5W, laser radiation tumor locus after administration 3h, the once irradiating time is 1min.Every 3d is administered once, altogether administration 6 times.In whole experimentation, observe mouse animation every day, 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.
In the time that water-soluble mono wall carbon nano tube-polymine/siRNA carrier system of 2 is tested in administration, the increase of the gross tumor volume of nude mice has obtained obvious inhibition compared with blank group.Merge after laser radiation, the increase of nude mice gross tumor volume has obtained more significantly suppressing.
In doing above-mentioned experiment, also adopt other near infrared sources and antitumor drug to do similar experiment, all obtain identical and similar result, the present invention's science of dividing into groups, method is reliable and stable, and other experimental results will not enumerate.
The invention provides a kind of water-soluble mono wall carbon nano tube and preparation method thereof, using 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, test result shows, Single Walled Carbon Nanotube soluble derivative in the present invention, water dispersible is strong, very low to the toxicity of organism, and physics and chemical stability are good, quality is good, the condition of preparation easily meets, 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 the carrier of a kind of good antitumor drug or gene, itself has minimum toxicity, and stronger is water-soluble, good biocompatibility, and specific surface area is large, 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 tumor tissues.
Water-soluble mono wall carbon nano tube provided by the invention can also have been given play to more outstanding anti-tumor activity in conjunction with near-infrared laser thermotherapy, test shows no matter be external or body in well generation and the development of inhibition tumor cell and related tissue in the situation that of thermotherapy.Expection can be used for the treatment of a kind of good thermotherapy sensitizer of tumour, can also serve as the transport vehicle of chemicals, protein, nucleic acid, is the innovation greatly in medicine preparation.
The present invention compared with prior art has following outstanding useful technique effect:
1) the water-soluble mono wall carbon nano tube in the present invention is to the characteristic of carbon nanotube itself without destruction, and water dispersible is strong, very low to the toxicity of organism, and physics and chemical stability are good, and quality is good, and the condition of preparation easily meets, 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, has minimum toxicity, and stronger is water-soluble, good biocompatibility, and specific surface area is large, and unreactiveness is high, has slow-releasing.
3) water-soluble mono wall carbon nano tube provided by the invention can also have been given play to more outstanding anti-tumor activity in conjunction with thermotherapy, when irradiating, near-infrared laser can bring into play antineoplastic activity, when not illumination, side effect is very little, can come optionally killing tumor cells tissue and cell according to means such as the focusing of laser.