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Nanometer prodrug used for anaerobic tumor treatment and capable of self-producing oxygen, singlet oxygen and active bivalent platinum through photoinduction, as well as preparation method and application of nanometer prodrug

A tumor treatment, singlet oxygen technology, applied in the field of biomedicine, can solve the problem of no anti-cancer effect, etc., and achieve the effect of improving tumor treatment effect, reversing resistance, and reducing toxic and side effects

Inactive Publication Date: 2017-11-24
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The object of the present invention is to provide a kind of amphiphilic photodynamic-chemotherapy combined nano-prodrug of light-induced self-production of oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors, so as to solve the problem of tumors in the prior art. The resistance of hypoxia to photodynamic therapy, and the lack of anticancer effect of oxygen transport materials themselves

Method used

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  • Nanometer prodrug used for anaerobic tumor treatment and capable of self-producing oxygen, singlet oxygen and active bivalent platinum through photoinduction, as well as preparation method and application of nanometer prodrug
  • Nanometer prodrug used for anaerobic tumor treatment and capable of self-producing oxygen, singlet oxygen and active bivalent platinum through photoinduction, as well as preparation method and application of nanometer prodrug
  • Nanometer prodrug used for anaerobic tumor treatment and capable of self-producing oxygen, singlet oxygen and active bivalent platinum through photoinduction, as well as preparation method and application of nanometer prodrug

Examples

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Embodiment 1

[0039] A preparation method of nano-prodrugs of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors according to Example 1, comprising the following steps:

[0040](1) will cis, trans, cis-[Pt(N 3 ) 2 (OH)(NH 3 ) 2 (O 2 CCH 2 CH 2 COOH)], N-hydroxysuccinimide (NHS, 1.5 equivalents) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 1.5 equivalents) were dissolved In dimethyl sulfoxide (DMSO), mix and stir overnight in the dark, then add the mixed solution dropwise to the DMSO solution of double-terminated amino polyethylene glycol (PEG), and react in the dark for 48 hours. Dialyze in ultrapure water for three days, and freeze-dry to obtain the reactant;

[0041] (2) Dissolve chlorin (Ce6), NHS (1.5 times equivalent) and EDC (1.5 times equivalent) in DMSO, mix and stir overnight in the dark, then slowly add the dissolved reactant therein, and stir in the dark for 48 Hours later, it was di...

Embodiment 2

[0046] A method for preparing a nano-prodrug of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors in Example 2, comprising the following steps:

[0047] (1) will anti, anti, anti-[Pt(N 3 ) 2 (OH)(methylamine)(Py)(O 2 CCH 2 CH 2 COOH)], N-hydroxysuccinimide (NHS, 1.5 equivalents) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 1.5 equivalents) were dissolved In dimethyl sulfoxide (DMSO), mix and stir overnight in the dark, then add the mixed solution dropwise to the DMSO solution of double-terminated amino polyethylene glycol (PEG), and react in the dark for 48 hours. Dialyze in ultrapure water for three days, and freeze-dry to obtain the reactant;

[0048] (2) Dissolve zinc phthalocyanine (ZnPc), NHS (1.5 times equivalent) and EDC (1.5 times equivalent) in DMSO, mix and stir overnight in the dark, then slowly add the dissolved reactants to it, and stir for 48 hours in the dark Afterwa...

Embodiment 3

[0052] A preparation method of nano-prodrugs of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors according to Example 3, comprising the following steps:

[0053] (1) the cis, trans, cis-[Pt(N 3 ) 2 (OH)(methylamine)(Py)(O2CCH2CH2COOH)], N-hydroxysuccinimide (NHS, 1.5 equivalents) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide salt acid salt (EDC, 1.5 times equivalent) was dissolved in dimethyl sulfoxide (DMSO), mixed and stirred overnight in the dark, and then the mixed solution was added dropwise to the DMSO solution of double-terminated amino polyethylene glycol (PEG), After 48 hours of reaction in the dark, dialyze in DMSO and ultrapure water for three days, and freeze-dry to obtain the reactant;

[0054] (2) Dissolve copper phthalocyanine (CuPc), NHS (1.5 times equivalent) and EDC (1.5 times equivalent) in DMSO, mix and stir overnight in the dark, then slowly add the dissolved reactants to it, and stir...

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Abstract

The invention discloses a nano-prodrug of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors. The nano-prodrug is a hydrophobic photosensitizer via a hydrophilic linker and Azido-containing tetravalent platinum [Pt(N 3 ) 2 (OH)(O 2 C(CH 2 ) n COOH)(Am1) 2 ] Linked amphiphilic photodynamic-chemotherapy combined anticancer prodrugs, self-assembled into nanoparticles in water, and loaded with up-conversion nanoparticles. The invention decomposes under the light of 980 nanometers to produce oxygen and divalent platinum with anticancer activity, and the oxygen produced by itself can be utilized by the photosensitizer in the prodrug to generate singlet oxygen, and finally singlet oxygen and anticancer activity The combination of active divalent platinum achieves the effect of photodynamic-chemotherapy combined therapy, thereby reversing the resistance of tumor hypoxic areas to photodynamic therapy and improving the therapeutic effect of tumors; at the same time, it is particularly stable in the absence of light and can reduce Toxic side effects on normal cells.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and particularly relates to an amphiphilic photodynamic-chemotherapy combined nano-prodrug of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors and a preparation method thereof, application. Background technique [0002] Hypoxia is one of the important characteristics of the microenvironment of solid tumors. The main reason for hypoxia is the malignant proliferation of tumor cells and the abnormal growth of tumor blood vessels. Due to the hypoxic environment of tumors, they are resistant to many treatment methods, such as: photodynamic therapy, chemotherapy and radiotherapy. In particular, photodynamic therapy kills tumor cells by depleting ambient oxygen to generate reactive oxygen species. Due to the low oxygen content in the tumor hypoxic environment, photodynamic therapy is often greatly reduced in efficacy. In order to ...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K33/24A61K47/69A61K47/60A61K47/55A61P35/00
CPCA61K41/0071A61K33/24A61K41/0076
Inventor 徐舒婷颜德岳朱新远黄卫周永丰
Owner SHANGHAI JIAO TONG UNIV
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