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Extracellular release monoclonal antibody carrier and preparation method thereof

A monoclonal antibody, cell technology, applied in the direction of antibodies, antibody medical components, anti-tumor drugs, etc., can solve problems such as easy endocytosis by cells, limited efficacy of monoclonal antibody drugs, and inability of monoclonal antibodies to function. To achieve the effect of reducing the proportion and inhibiting endocytosis

Pending Publication Date: 2021-03-09
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to their size, these protein-loaded nanoscale carriers are often easily endocytosed by cells.
The target of the monoclonal antibody in the carrier is not inside the cell, but on the surface of the cell membrane, so the endocytosed monoclonal antibody cannot exert its effect
This uncontrolled endocytosis limits the efficacy of monoclonal antibody drugs

Method used

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  • Extracellular release monoclonal antibody carrier and preparation method thereof
  • Extracellular release monoclonal antibody carrier and preparation method thereof
  • Extracellular release monoclonal antibody carrier and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0032] 20 mg of enzyme-responsive polypeptide was dissolved in 1 mL of boric acid-sodium borate (pH 8.0) buffer, and 100 mg of N-acryloyloxysuccinimide (NAS) was dissolved in 1 mL of dimethyl sulfoxide (DMSO). Add 80uL NAS solution to the enzyme-responsive polypeptide solution, and keep stirring, adjust the pH of the reaction solution to 8.5 with 1M sodium hydroxide (NaOH) solution, react at 4°C for 12h, and then dialyze PBS with a dialysis bag with a molecular weight cut-off of 300 48 hours, freeze-dried for 48 hours to obtain a double acrylamidated enzyme-responsive polypeptide.

[0033] Synthesis of extracellular release monoclonal antibody carrier: Dissolve Nimotuzumab monoclonal antibody in phosphate buffered saline (PBS) under nitrogen atmosphere, and add N-(3-aminopropyl)methacrylic acid to it in sequence salt (APM), 2-methacryloyloxyethylphosphorylcholine (MPC), bisacrylamidase-responsive polypeptide, tetramethylethylenediamine (TEMED), stirred at 4°C for 15min, and th...

Embodiment example 2

[0035] Synthesis of double acrylamidase-responsive peptides: Dissolve 40 mg of enzyme-responsive peptides in 2 mL of boric acid-sodium borate (pH 8.0) buffer, dissolve 200 mg of N-acryloxysuccinimide (NAS) in 2 mL of diacrylamide in methyl sulfoxide (DMSO). Add 0.2mL NAS solution to the enzyme-responsive polypeptide solution, and keep stirring, adjust the pH of the reaction solution to 8.2 with 1M sodium hydroxide (NaOH) solution, react at 10°C for 8h, and then use a dialysis bag with a molecular weight cut-off of 500 for PBS Dialyzed for 42 hours, freeze-dried for 50 hours to obtain the double acrylamidated enzyme-responsive polypeptide.

[0036] Synthesis of extracellular release monoclonal antibody carrier: Dissolve trastuzumab monoclonal antibody in phosphate buffered saline (PBS) under argon atmosphere, and add N-(3-aminopropyl)methyl Acrylate (APM), 2-methacryloyloxyethylphosphorylcholine (MPC), bisacrylamidase-responsive polypeptide, tetramethylethylenediamine (TEMED),...

Embodiment 3

[0038] Synthesis of double acrylamidase-responsive peptides: Dissolve 30 mg of enzyme-responsive peptides in 1.5 mL of boric acid-sodium borate (pH8.0) buffer, and dissolve 150 mg of N-acryloyloxysuccinimide (NAS) in 1.5 mL dimethyl sulfoxide (DMSO). Add 0.15mL NAS solution to the enzyme-responsive polypeptide solution, and keep stirring, adjust the pH of the reaction solution to 8.0 with 1M sodium hydroxide (NaOH) solution, react at 4°C for 12h, and then use a dialysis bag with a molecular weight cut-off of 350 for PBS Dialyzed for 48 hours, and freeze-dried for 48 hours to obtain a bisacrylamidated enzyme-responsive polypeptide.

[0039]Synthesis of extracellular release monoclonal antibody carrier: Dissolve cetuximab monoclonal antibody in phosphate buffered saline (PBS) under nitrogen atmosphere, and add N-(3-aminopropyl)methacrylic acid to it in sequence salt (APM), 2-methacryloyloxyethylphosphorylcholine (MPC), bisacrylamidase-responsive polypeptide, tetramethylethylene...

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Abstract

The invention discloses an extracellular release monoclonal antibody carrier and a preparation method thereof. A monoclonal antibody, an electropositive monomer, a phosphorylcholine-rich monomer and across-linking agent bisacrylamide enzyme-responsive polypeptide are uniformly mixed; the monomer is enriched on the surface of the monoclonal antibody through static electricity and hydrogen bond acting force; then, in-situ free radical polymerization is initiated through a water-soluble free radical initiation system; and thus, a high-molecular cross-linked network shell layer which is rich in phosphorylcholine and has enzyme responsiveness, is formed on the surface of the monoclonal antibody. The carrier disclosed by the invention has enzyme responsiveness, can effectively inhibit endocytosis, and can be degraded in a tumour microenvironment, so that extracellular release of the monoclonal antibody can be realized, and the carrier is applied to tumour treatment.

Description

technical field [0001] The invention relates to the technical field of preparation of monoclonal antibody carriers, and more specifically relates to extracellular release of monoclonal antibody carriers and a preparation method thereof. Background technique [0002] At present, monoclonal antibodies have become an indispensable protein drug for clinical treatment of tumors. It has high specificity and high safety, and since most monoclonal antibodies act on the receptors on the cell membrane, there is no need to cross the cell membrane and escape from endosomes, so the efficiency of monoclonal antibody therapy is relatively high. However, as a protein drug, its practical application is limited by its own protein structure, such as its fragile quaternary structure is easily destroyed, resulting in inactivation, and in the in vivo environment, it is easy to degrade, and inactivation or degradation The protein fragments will further cause an immune response, with greater side ...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/32A61K47/42A61K39/395A61P35/00
CPCA61K9/5169A61K9/5138A61K39/39558A61P35/00
Inventor 原续波李思迪赵瑾侯信
Owner TIANJIN UNIV
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