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Macrophage membrane coated arginine deiminase/catalase/IR780 nanoparticle, preparation method and application

An arginine deiminase and catalase technology, applied in biochemical equipment and methods, oxidoreductases, enzymes, etc., can solve the problems of poor stability, low bioavailability, poor targeting, etc. Effects of poor stability, high immunogenicity, and short half-life

Active Publication Date: 2021-12-07
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles overcome the shortcomings of arginine deiminase, such as poor stability, easy to be degraded by enzymes, low bioavailability, and poor targeting. Through the active recognition of chemokines and signaling molecules released by the tumor area by the endogenous biomacromolecules on the surface of the macrophage cell membrane in vivo, nanoparticles are recruited to the tumor area, thereby increasing the accumulation of drugs in the tumor tissue. The photothermal therapy effect of the agent or the photodynamic therapy effect of the photosensitizer can play an anticancer effect

Method used

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  • Macrophage membrane coated arginine deiminase/catalase/IR780 nanoparticle, preparation method and application
  • Macrophage membrane coated arginine deiminase/catalase/IR780 nanoparticle, preparation method and application
  • Macrophage membrane coated arginine deiminase/catalase/IR780 nanoparticle, preparation method and application

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Embodiment 1

[0032] Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles include arginine deiminase / catalase / IR780 nanoparticles and macrophage membrane coating. Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles formula has the weight-to-number ratio of each component: 4.5 parts of hyaluronic acid, 2.5 parts of hydroxypropyl-β-cyclodextrin, 3 parts of lecithin, 1 part of cholesterol, 1 part of distearoylphosphatidylethanolamine-polyethylene glycol 2000, 200 parts of bis(2-hydroxyethylamino)tris(hydroxymethyl)methane-hydrochloride buffer, The buffer concentration is 50 mM, the buffer pH is 6.5, the content of arginine deiminase is 0.1 mg / mL, the content of catalase is 0.05 mg / mL, and the content of IR780 is 0.01 mg / mL.

[0033]Preparation method: (1) The preparation method of HA-HCD: dissolve the hyaluronic acid of prescription amount in anhydrous formamide, add 1-ethyl-3-[3-(dimethylamino)propyl]carbodiethylene After stirring the amine hydroc...

Embodiment 2

[0035] Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles include arginine deiminase / catalase / IR780 nanoparticles and macrophage membrane coating. Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles formula has the weight-to-number ratio of each component: 5.1 parts of hyaluronic acid, 3.1 parts of hydroxypropyl-β-cyclodextrin, 5.0 parts of lecithin, 2.8 parts of cholesterol, 2.0 parts of distearoylphosphatidylethanolamine-polyethylene glycol 5000, 636 parts of dipotassium hydrogen phosphate-phosphate buffer, the buffer concentration is 120mM, the buffer pH is 6.0, arginine The content of acid deiminase is 0.1 mg / mL, the content of catalase is 0.15 mg / mL, and the content of IR780 is 0.02 mg / mL.

[0036] Preparation method: (1) The preparation method of HA-HCD: dissolve the hyaluronic acid of prescription amount in anhydrous formamide, add 1-ethyl-3-[3-(dimethylamino)propyl]carbodiethylene After stirring the amine hydrochloride in...

Embodiment 3

[0038] Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles include arginine deiminase / catalase / IR780 nanoparticles and macrophage membrane coating. Macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles formula has the following weight-to-number ratios of components: 5.6 parts of hyaluronic acid, 3.5 parts of hydroxypropyl-β-cyclodextrin, 5.6 parts of lecithin, 3.6 parts of cholesterol, 1 part of distearoylphosphatidylethanolamine-polyethylene glycol 2000, 1.1 parts of distearoylphosphatidylethanolamine-polyethylene glycol 5000, tris-hydrochloric acid 690 copies of salt buffer solution, the buffer concentration is 130mM, the buffer solution pH is 6.3, the content of arginine deiminase is 0.1mg / mL, the content of catalase is 0.12mg / mL, and the content of IR780 is 0.03mg / mL mL.

[0039] Preparation method: (1) The preparation method of HA-HCD: dissolve the hyaluronic acid of prescription amount in anhydrous formamide, add 1-ethyl-3-[3-...

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Abstract

The invention belongs to the field of pharmaceutical preparations. The invention relates to a preparation method and application of a macrophage membrane coated arginine deiminase / catalase / IR780 nanoparticle. The prepared macrophage membrane coated arginine deiminase / catalase / IR780 nanoparticle is good in biocompatibility, the preparation method is simple, the particle size distribution of the nanoparticle is uniform, the stability of the arginine deiminase can be improved, the protease hydrolysis resistance ability of the arginine deiminase is improved, an anti-tumor effect is enhanced in cooperation with photothermal therapy or photodynamic therapy, and a potential application value is achieved in the fields of treatment of cancers (especially arginine-dependent diseases) and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to macrophage membrane-coated arginine deiminase / catalase / IR780 nanoparticles, a preparation method and application. Background technique [0002] Tumor metabolism, a target for the treatment of certain malignancies, has become the focus of attention in recent years. Amino acid deprivation therapy, which degrades or deprives tumors of essential amino acids for survival based on metabolic enzymes, is a typical representative and has been successfully applied in clinical trials. As one of the conditionally essential amino acids, arginine is derived from the conversion and synthesis of citrulline through two key enzymes, arginine succinate synthase (ASS1) and arginine succinate lyase, which play a role in cell division and metabolism. Key role. The growth and proliferation of some malignant tumor cells must rely on exogenous arginine, and the loss of the key rate-limiting enz...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K38/50A61K9/51A61K47/36A61K47/40A61K47/24A61K47/28A61P35/00A61K38/44
CPCA61K9/5176A61K9/5161A61K9/5192A61K9/5146A61K9/5123A61K38/44A61K38/50A61K41/0052A61K41/0057C12Y111/01006A61P35/00C12Y305/03006A61K2300/00Y02A50/30
Inventor 张景勍吴艳袁子怡杨强张霞吴诗情
Owner CHONGQING MEDICAL UNIVERSITY
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