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Preparation method and applications of photo-thermal and photodynamic co-used antitumor drug delivery system taking gold nano star mediated by folic acid as carrier

A delivery system and gold nanotechnology, applied in the field of medicine, can solve the problems of poor biocompatibility, large toxic and side effects, and poor targeting, and achieve the effects of low cost, small toxic and side effects, and simple preparation process.

Inactive Publication Date: 2015-08-12
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In view of the above situation, in order to overcome the defects of the prior art, the purpose of the present invention is to provide a preparation method and application of a drug delivery system with folic acid-mediated gold nanostars as the carrier of photothermal and photodynamic combined anti-tumor, which can effectively Solve the problems of existing anti-tumor drugs with large toxic and side effects, poor biocompatibility and poor targeting

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0026] In concrete implementation, the present invention can be realized by the following steps:

[0027] (1) Preparation of aminated gold nanostar solution: Add 20 mL of gold nanostar solution with a concentration of 50 μg / mL at 25 °C under magnetic stirring conditions of 540 r / min, and then add NH with a concentration of 1 mg / mL 2 - 1 mL of PEG2000-SH solution, stirred at room temperature and protected from light for 12 hours, then centrifuged at 10,000 rpm for 30 minutes to obtain a precipitate, which was redissolved in 21 mL of ultrapure water to obtain an aminated gold nanostar (GNSTs-PEG) solution;

[0028] (2) Preparation of targeted gold nanostars: Weigh 19.91 mg of folic acid, 13.94 mg of N,N'-dicyclohexylcarbimide, and 10.36 mg of N-hydroxysuccinimide (weight ratio: folic acid : N,N'-dicyclohexylcarboimide: N-hydroxysuccinimide=1︰0.7︰0.52), then add to 4mL dimethyl sulfoxide in turn, mix and dissolve, and then activate the carboxyl group, that is React at 50°C and 4...

Embodiment 2

[0032] In concrete implementation, the present invention can be realized by the following steps:

[0033] (1) Preparation of aminated gold nanostars: Add 15 mL of gold nanostar solution with a concentration of 50 μg / mL, and then add 3 mL of PEI-SH with a concentration of 5 mg / mL at 20 °C and 600 r / min magnetic stirring conditions, Stir the reaction in the dark for 8 hours, then centrifuge at a high speed of 10000 rpm for 30 minutes, and then redissolve with ultrapure water to obtain an aminated gold nanostar solution;

[0034] (2) Preparation of targeted gold nanostars: Weigh 18 mg of folic acid, 12 mg of N, N'-dicyclohexylcarbimide, and 9 mg of N-hydroxysuccinimide, and then add 4 mL of phosphate buffer in sequence In, mix and dissolve, and then activate the carboxyl group, that is, at 45 ° C, 500r / min, shielded from light and magnetically stirred for 16 hours, then centrifuge the resulting solution at 10,000 rpm for 30 minutes to obtain a precipitate, which is redissolved wi...

Embodiment 3

[0038] In specific implementation, the present invention can also be realized by the following steps:

[0039] (1) Preparation of aminated gold nanostars: Add 15 mL of gold nanostar solution with a concentration of 50 μg / mL, and then add 3 mL of amino compounds with a concentration of 5.0 mg / mL under the condition of 21 ° C and 510 r / min magnetic stirring, Stir the reaction in the dark for 9 hours, then centrifuge at a high speed of 10000 rpm for 30 minutes, and then redissolve with ultrapure water to obtain an aminated gold nanostar solution;

[0040] (2) Preparation of targeted gold nanostars: Weigh 17.5 mg of folic acid, 12.5 mg of N, N'-dicyclohexyl carboximide, and 9 mg of N-hydroxysuccinimide, and then add 3.5 mL of them in turn to react In the solution, mix and dissolve, and then activate the carboxyl group, that is, at 45°C and 510r / min to avoid light and magnetically stir for 16h, then centrifuge the resulting solution at 10,000 rpm for 30min to obtain a precipitate, ...

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Abstract

The invention relates to a preparation method and applications of a photo-thermal and photodynamic co-used antitumor drug delivery system taking gold nano star mediated by folic acid as the carrier. In the prior art, the antitumor drugs have adverse side and toxic effects, moreover, the biocompatibility and targeting performance of the antitumor drugs are bad, and the provided system solves the problems mentioned above. In the preparation method, reaction active amino and carboxylic groups are grafted onto the surface of gold nano stars through covalent bonds, then targeting molecules are connected to the gold nano stars through amidation reactions to obtain a targeting gold nano star solution; then the amino groups on the end of the targeting compounds carry out chemical reactions with near-infrared fluorescence probes so as to obtain a gold nano star solution with functions of folic acid targeting and near-infrared fluorescence imaging; and finally an antitumor drug (adriamycin) is directly loaded on the surfaces of gold nano stars through an electrostatic adsorption effect. The chemical stability and physical stability of the drug delivery system are both very good, the preparation technology is simple, the resources of the raw materials are abundant, the cost is low, the side and toxic effect is little, and the tumor cell proliferation can be effectively inhibited.

Description

technical field [0001] The invention relates to medicine, in particular to a preparation method and application of a drug delivery system using folic acid-mediated gold nanostar as a carrier for combined photothermal and photokinetic anti-tumor. Background technique [0002] Photothermal therapy (Photo-thermal Therapy, PTT) is to change the environment of tumor cells by heating, so that tumor cells can degenerate and necrosis, so as to achieve the purpose of treatment. For example, various gold nanostructures, including gold nanorods , nanoshells, nanocages, hollow nanospheres, especially branched gold nanostars, have been proven to have surface plasmon resonance properties in the near-infrared region, and thus generate excessive heat through near-infrared laser irradiation, thereby killing tumor cells. [0003] Photodynamic therapy (Photodynamic Therapy, PDT) is the use of tumor cells to selectively absorb photosensitizers, and then use non-thermal lasers of specific wavele...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K41/00A61K31/704A61K49/00A61P35/00
Inventor 王蕾孟德辉郝永伟张兵详张潘潘史进进赵亚林李懂张振中张云
Owner ZHENGZHOU UNIV
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