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Tumor-targeted nanocapsule and preparation method and application thereof

A technology of nano-microcapsules and tumor microenvironment, applied in the field of tumor-targeting nano-microcapsules and their preparation

Inactive Publication Date: 2018-12-25
TIANJIN NANUO BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, based on the complexity of tumors, there are still many difficulties to be overcome in the development of targeted nanocapsules with clinical value.

Method used

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  • Tumor-targeted nanocapsule and preparation method and application thereof
  • Tumor-targeted nanocapsule and preparation method and application thereof
  • Tumor-targeted nanocapsule and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Preparation and Characterization of Nimotuzumab Nanocapsules Containing MMP-2 Degradable Crosslinker

[0063] Take a solution (200 μL) containing 1 mg of Nimotuzumab, add N-(3-aminopropyl)methacrylate, the mole of Nimotuzumab to N-(3-aminopropyl)methacrylate The ratio is 1:300, then add 2-methacryloyloxyethylphosphorylcholine, the molar ratio of nimotuzumab to 2-methacryloyloxyethylphosphorylcholine is 1:4000; then press The molar ratio of Nimotuzumab to the cross-linking agent is 1:500. Add matrix metalloproteinase-2 degradable polypeptide cross-linking agent, let it stand for 10 minutes, and use electrostatic and hydrogen bonding to enrich the monoclonal antibody. Reactive monomer and enzyme-degradable polypeptide cross-linking agent; then add ammonium persulfate and tetramethylethylenediamine, the molar ratio of nimotuzumab to ammonium persulfate and tetramethylethylenediamine is 1:500:1000 , and reacted at 4°C for 2 hours to prepare poly-2-methacryloylo...

Embodiment 2

[0071] Example 2 Encapsulated specific BsAbs containing pH-sensitive cross-linkers Preparation and Characterization of Nanocapsules

[0072] Take a solution (200 μL) containing 1 mg of double antibody, add acrylamide monomer, The molar ratio to acrylamide is 1:300, then add 2-methacryloyloxyethylphosphorylcholine, the molar ratio of double antibody to 2-methacryloyloxyethylphosphorylcholine is 1:4000; then Then add ethylene glycol dimethacrylate crosslinking agent according to the ratio of the molar ratio of the double antibody to the crosslinking agent of 1:500, let it stand for 10 minutes, and use the hydrogen bond to enrich the reaction monomer around the double antibody and pH sensitive cross-linking agent; then add ammonium persulfate and tetramethylethylenediamine, the molar ratio of double antibody to ammonium persulfate and tetramethylethylenediamine is 1:500:1000, react at 4°C for 2h, Preparation of nanocapsules loaded with specific bis-antibody containing pH-se...

Embodiment 3

[0074] Example 3 Preparation and Characterization of Cetuximide-Encapsulated Nanocapsules Containing Redox-Sensitive Crosslinkers

[0075] Take a solution (200 μL) containing 1 mg of cetuximab, add acrylamide monomer, the molar ratio of cetuximab to acrylamide is 1:300, and then add 2-methacryloyloxyethylphosphorylcholine , the molar ratio of cetuximab to 2-methacryloyloxyethyl phosphorylcholine is 1:4000; Allyl disulfide cross-linking agent, let it stand for 10 minutes, and use hydrogen bonding to enrich the reaction monomer and redox-sensitive cross-linking agent around the cetuximab; then add ammonium persulfate and tetramethylethylene disulfide Amine, the molar ratio of cetuximab to ammonium persulfate and tetramethylethylenediamine is 1:500:1000, react at 4°C for 2 hours, and prepare redox-sensitive cross-linking agent-loaded cetuximab resistant nanocapsules.

[0076] The nano-microcapsules loaded with cetuximab prepared above were observed by transmission electron mi...

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Abstract

The invention provides a tumor-targeted nanocapsule and a preparation method and application thereof. The tumor-targeted nanocapsule comprises a tumor microenvironmental-sensitive polymer-encapsulatedsubstance with anti-tumor activity, a tour diagnostic reagent or a developer; a tumor microenvironmental-sensitive polymer includes a tumor microenvironmental-sensitive cross-linking agent and 2-methacryloxyethyl phosphate choline, and the tumor microenvironmental-sensitive crosslinking agent at least includes an enzyme degradable polypeptide cross-linking agent over-expressed in the tumor microenvironment; the enzyme degradable polypeptide cross-linking over-expressed in the tumor microenvironment is preferably one or more of matrix metalloproteinase-degradable polypeptide cross-linking agents and hyaluronidase-degradable polypeptide cross-linking agents, and more preferably one or more of the matrix metalloproteinase-degradable polypeptide cross-linking agents. The tumor-targeted nanocapsule is small and uniform in particle size, packaged drugs and reagents can be delivered and released in a targeted manner in the tumor-targeted microenvironment, and long circulation in the blood isachieved.

Description

technical field [0001] The invention belongs to the fields of biomedicine, pharmacy and polymer materials, and specifically relates to a tumor-targeting nano-microcapsule based on the characteristics of the tumor microenvironment and its preparation method and application. Background technique [0002] The ultimate goal of malignant tumor treatment is to increase the survival time of patients and improve the quality of life by reducing the systemic toxicity of drugs. The targeted delivery and release of drugs is the key link to improve efficacy and reduce toxicity. One of the important branches is nano-microcapsules loaded with anti-tumor active substances. [0003] In blood vessels of normal tissues, the distance between two endothelial cells is about 2 nm, while in tumor blood vessels, the distance between two endothelial cells is 100-150 nm. This structural feature leads to enhanced permeability resistance of tumor tissues. Hysteresis effect (enhanced permeability and re...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K45/00A61K49/00A61P35/00
CPCA61K9/5169A61K45/00A61K49/00A61K9/51A61K39/395A61K47/32A61P35/00
Inventor 原续波康春生卢云峰
Owner TIANJIN NANUO BIO TECH CO LTD