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A kind of photodynamic therapy deep tumor targeted nano-photosensitizer and preparation method thereof

A photodynamic therapy and tumor targeting technology, applied in antitumor drugs, pharmaceutical formulations, medical preparations containing active ingredients, etc. Toxicity, saving treatment cost, good effect

Active Publication Date: 2021-06-11
广西康健奥鑫生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Using the existing clinical X-ray equipment, low-dose irradiation of targeted nano-photosensitizers can generate active oxygen and generate photodynamic effects, which can solve the problems that existing photodynamic therapy cannot perform photodynamic therapy on deep tumors and skin phototoxicity, Mild reaction conditions, industrialized manufacturing, energy saving and environmental protection, can promote the development of the sericulture industry chain towards high value-added industries

Method used

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  • A kind of photodynamic therapy deep tumor targeted nano-photosensitizer and preparation method thereof
  • A kind of photodynamic therapy deep tumor targeted nano-photosensitizer and preparation method thereof
  • A kind of photodynamic therapy deep tumor targeted nano-photosensitizer and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0047] Embodiment 1: Preparation of copper protein targeting nano photosensitizer with human serum albumin raw material

[0048] To prepare a human serum albumin solution, add 100 mg of raw materials into water for injection to dissolve, stir at room temperature, and dilute to 4%. After centrifugation, take the supernatant, adjust the pH to 10, add soluble copper dichloride with a material ratio of mercapto: copper = 2:0.9, stir and mix evenly at room temperature to obtain a blue copper protein solution, add twice The reduction of ascorbic acid in the amount of copper species gives a colorless copper protein chelate solution. Add 2% bismaleimide polyethylene glycol (MAL-PEG-MAL, molecular weight 3K) and 2 mg of 13 amino acid targeting polypeptides connected with sulfhydryl groups, 1 mg of {d-CYS}{d-ARG} {GLY}{d-ASP}{d-LYS} membrane-penetrating peptide, stirred at room temperature for 4.5 hours, removed impurities by conventional methods such as ultrafiltration and nanofiltrat...

Embodiment 2

[0050] Embodiment 2: Preparation of copper polypeptide-targeted nano-photosensitizer with polypeptide raw materials

[0051] Weigh 1 part of glutathione and dissolve it in 80 times pure water, stir at room temperature, adjust the pH value to 8.5 with acid and alkali, add copper nitrate solution with a ratio of 1 / 2 of the substance, and stir at room temperature to form a blue copper polypeptide solution. Add twice ascorbic acid reduction of the amount of copper substance, obtain colorless copper polypeptide photosensitizer solution, add 5mmol / L genipin solution, add 1% bismaleimide polyethylene glycol (MAL-PEG-MAL , with a molecular weight of 3.4k), 2 mg of a tumor-targeting polypeptide containing a sulfhydryl group, and 1 mg of a membrane-penetrating peptide containing a sulfhydryl group were stirred at room temperature for 4 hours, and impurities were removed by conventional ultrafiltration to obtain a copper polypeptide-targeted photosensitizer, which was lyophilized into Po...

Embodiment 3

[0054] Weigh 1 part of glutathione and dissolve it in 20 times of pure water, stir at room temperature, adjust the pH to 10.5 with an acid-base regulator, add copper salt of glutathione in the amount of 1 / 2 of the substance, stir at room temperature, and form blue Color copper polypeptide solution, add glucose twice the amount of copper salt substance and fructose reduction of twice the amount of copper salt substance, stir at room temperature to obtain a colorless copper polypeptide photosensitizer solution, add 1.5% bisphosphonate with a molecular weight of 10K Maleimide polyethylene glycol MAL-PEG-MAL, (regular and extraordinary only one kind can be added) stir at room temperature, add the same amount of maleimide polyethylene glycol, which has been connected at one end 2 mg of a thiol-based tumor-targeting polypeptide (2% of the total reactants), 1 mg of the penetrating peptide (1% of the total reactants), stirred at room temperature for 6 hours, dialyzed by conventional me...

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Abstract

A targeted nano-photosensitizer for photodynamic therapy of deep tumors and its preparation method, using protein, polypeptide or amino acid to react with a soluble copper salt solution, and then reducing to obtain a monovalent protein chelated targeted nano-photosensitizer, polypeptide copper chelated Or amino acid copper chelation targeted nano photosensitizer. The targeted nano-photosensitizer can generate strong fluorescence under X-ray excitation far lower than the dose of ordinary radiotherapy, and has photodynamic therapy effect on tumors. The targeted nano-photosensitizer has small particle size, good water solubility, low toxic and side effects, and is easily endocytosed by deep tumor cells. At the same time, the excitation light source of the targeted nano-photosensitizer is X-rays, which has high treatment efficiency and can solve the problems that existing photodynamic therapy cannot perform photodynamic therapy on deep tumors and skin phototoxicity. The photosensitizer has mild reaction conditions, can be manufactured industrially, is energy-saving and environment-friendly, can promote the development of sericulture industry chains towards high value-added industries, and has good economic, social and ecological benefits.

Description

technical field [0001] The invention belongs to the technical field of biological targeting nano-medicine, in particular to a targeted nano-photosensitizer for photodynamic therapy of deep tumors and a preparation method thereof. Background technique [0002] my country is one of the countries with high incidence of tumor diseases, and about a quarter of cancer deaths in the world occur in China. Deep tumors in the body, such as primary cellular hepatocellular carcinoma (HCC), ranks second among high-mortality tumors in my country. Most HCC patients in my country have a background of hepatitis B and liver cirrhosis. The onset is hidden, and early symptoms are mostly not obvious. Early detection The rate is low, surgical margins are difficult to define, postoperative recurrence rate is high, chemotherapy and postoperative chemotherapy are not highly targeted and toxic. Therefore, improving the targeting of deep tumor treatment, reducing skin phototoxicity with minimally invas...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/14A61P35/00
Inventor 聂国朝吴艳华潘心红王约罗思强
Owner 广西康健奥鑫生物医药科技有限公司
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