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A tumor microenvironment-responsive nuclear-targeted platinum nanoparticle and its preparation method and application

A tumor microenvironment, platinum nanotechnology, applied in antitumor drugs, nanotechnology, nanotechnology, etc., can solve the problems of poor targeting of small molecule drugs and limited efficacy in advanced HCC

Active Publication Date: 2020-10-23
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the curative effect of traditional chemotherapy on advanced HCC is extremely limited, because many small-molecule drugs have poor targeting and are difficult to accumulate in the tumor site to exert their drug effect

Method used

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  • A tumor microenvironment-responsive nuclear-targeted platinum nanoparticle and its preparation method and application
  • A tumor microenvironment-responsive nuclear-targeted platinum nanoparticle and its preparation method and application
  • A tumor microenvironment-responsive nuclear-targeted platinum nanoparticle and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1) Synthesis of a pH-sensitive amphiphilic polymer: 0.5 g of ethylene glycol acrylate copolymer and 0.05 g of mercaptoethylamine were dissolved in 5 ml of dimethyl sulfoxide, and under the protection of argon, drop Add 460 μl of triethylamine and stir at room temperature for 24 hours. After the reaction, the solution was dialyzed in water and freeze-dried to obtain a β-mercapto-modified ethylene glycol acrylate copolymer (a pH-sensitive amphiphilic polymer). NMR structural characterization of the prepared pH-sensitive amphiphilic polymer, such as figure 1 shown.

[0042]2) Synthesis of ultra-small platinum nanoparticles: 72 mg of chloroplatinic acid and 0.8 g of polyacrylic acid were dissolved in 38 ml of water, and stirred at room temperature for 30 minutes. Add 5 mg of sodium borohydride and continue stirring for 1 hour, dialyze the reaction solution in water to obtain ultra-small platinum nanoparticles. The prepared ultra-small platinum nanoparticles were characte...

Embodiment 2

[0045] 1) Synthesis of a pH-sensitive amphiphilic polymer: 0.5 g of ethylene glycol acrylate copolymer and 0.05 g of mercaptoethylamine were dissolved in 5 ml of dimethyl sulfoxide, and under the protection of argon, drop Add 460 μl of triethylamine and stir at room temperature for 24 hours. After the reaction, the solution was dialyzed in water and freeze-dried to obtain a β-mercapto-modified ethylene glycol acrylate copolymer. NMR structural characterization of the prepared pH-sensitive amphiphilic polymer, such as figure 1 shown.

[0046] 2) Synthesis of ultra-small platinum nanoparticles: 72 mg of chloroplatinic acid and 0.8 g of polyacrylic acid were dissolved in 38 ml of water, and stirred at room temperature for 30 minutes. Add 5 mg of sodium borohydride and continue stirring for 1 hour, dialyze the reaction solution in water to obtain ultra-small platinum nanoparticles. The prepared ultra-small platinum nanoparticles were characterized by TEM and XRD, as shown in ...

Embodiment 3

[0049] 1) Synthesis of a pH-sensitive amphiphilic polymer: 0.5 g of ethylene glycol acrylate copolymer and 0.05 g of mercaptoethylamine were dissolved in 5 ml of dimethyl sulfoxide, and under the protection of argon, drop Add 460 μl of triethylamine and stir at room temperature for 24 hours. After the reaction, the solution was dialyzed in water and freeze-dried to obtain a β-mercapto-modified ethylene glycol acrylate copolymer. NMR structural characterization of the prepared pH-sensitive amphiphilic polymer, such as figure 1 shown.

[0050] 2) Synthesis of ultra-small platinum nanoparticles: 72 mg of chloroplatinic acid and 0.8 g of polyacrylic acid were dissolved in 38 ml of water, and stirred at room temperature for 30 minutes. Add 5 mg of sodium borohydride and continue stirring for 1 hour, dialyze the reaction solution in water to obtain ultra-small platinum nanoparticles. The prepared ultra-small platinum nanoparticles were characterized by TEM and XRD, as shown in ...

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Abstract

The invention discloses tumor microenvironment response type nucleus-targeting platinum nanoparticles comprising platinum nanoparticles and nucleus-targeting peptide and amphiphilic polymer modified on the platinum nanoparticles. The invention further discloses a preparation method of the tumor microenvironment response type nucleus-targeting platinum nanoparticles. The preparation method comprises the steps as follows: a platinum salt precursor and a blocking agent are dissolved in water to form a precursor solution, and a strong reducing agent is added for a reduction reaction to obtain subminiature platinum nanoparticles; amphiphilic polymers are dissolved in a good solvent, a modifier is added, and stirring reaction is conducted to obtain a n amphiphilic polymer is obtained; the subminiature platinum nanoparticles and nucleus-targeting polypeptide are dissolved in water, and stirring reaction is conducted to prepare nucleus-targeting platinum nanoparticles; and the nucleus-targeting platinum nanoparticles and the amphiphilic polymer are dissolved in water, and stirring reaction is conducted to obtain the tumor microenvironment response type nucleus-targeting platinum nanoparticles. The tumor microenvironment response type nucleus-targeting platinum nanoparticles can specifically target tumor cells, center cell nucleus to damage DNA and kill tumor cells.

Description

technical field [0001] The invention relates to the field of preparation of tumor microenvironment-responsive nuclear-targeted platinum nanoparticles, in particular to a preparation method, product and application of pH-responsive nuclear-targeted ultra-small platinum nanoparticles. Background technique [0002] Liver cancer (Hepatocellular Carcinoma, HCC) is one of the most common malignant tumors in the world. According to data from the China Cancer Registry Center in 2017, the number of liver cancer cases in my country is approximately 365,000, ranking fourth in the number of cancer cases; and the number of deaths is approximately 319,000, ranking second. As the second leading cause of cancer-related death, liver cancer is a serious threat to human life and health all over the world, especially in underdeveloped countries. [0003] Patients with early liver cancer can undergo surgical resection of liver tumor tissue, but the difficulty of early diagnosis and the rapid de...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/58A61K47/59A61K47/64A61K47/69A61K33/243A61P35/00B82Y5/00
CPCA61K47/58A61K47/59A61K47/64A61K47/6929A61P35/00A61K33/243B82Y5/00
Inventor 凌代舜李方园廖红卫任家凤李锐清
Owner ZHEJIANG UNIV
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