Antibody synthetic bacteria-nano stimulant heterozygote system and application thereof

A stimulant, nano-technology, applied in the application field of cytokine nano-stimulator, antibody synthetic bacteria-nano-stimulator hybrid system, can solve problems affecting the function and activity of living cells, and achieve immune-related adverse reactions Severe, addressing effects of low immune response rates

Pending Publication Date: 2022-04-15
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, traditional chemical reactions will affect the function and activity of living cells, causing irreversible effects

Method used

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  • Antibody synthetic bacteria-nano stimulant heterozygote system and application thereof
  • Antibody synthetic bacteria-nano stimulant heterozygote system and application thereof
  • Antibody synthetic bacteria-nano stimulant heterozygote system and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Embodiment 1: Mal-poly(PEG 77 -co-His) preparation

[0095] Michael addition reaction to prepare tumor extracellular pH-responsive copolymers, such as figure 2 shown. Weigh a certain amount of 1,6-hexanediol diacrylate (HDDA), histamine (His) and maleimide-polyethylene glycol amino (Mal-PEG 77 -NH 2 ) were mixed in a molar ratio of 1:0.85:0.15 and dissolved in a certain volume of dimethyl sulfoxide (DMSO), reacted for 48 hours at 55°C in an argon atmosphere, purified and freeze-dried to obtain a polymer powder. The copolymer is further analyzed and identified by gel permeation chromatography / NMR.

Embodiment 2

[0096] Embodiment 2: DBCO-poly(PEG 77 -co-His) preparation

[0097] Michael addition reaction to prepare tumor extracellular pH-responsive copolymers, such as image 3 shown. Weigh a certain amount of 1,6-hexanediol diacrylate (HDDA), histamine (His) and diphenylcyclooctyne-polyethylene glycol amino (DBCO-PEG 77 -NH 2 ) were mixed in a molar ratio of 1:0.85:0.15 and dissolved in a certain volume of dimethyl sulfoxide (DMSO), reacted for 48 hours at 55°C in an argon atmosphere, purified and freeze-dried to obtain a polymer powder. The copolymer is further analyzed and identified by gel permeation chromatography / NMR.

Embodiment 3

[0098] Example 3: Preparation of Mal-labeled IL-12 nano-stimulator

[0099] Preparation of IL-12 nano-stimulator by microemulsion method: 10 μg of IL-12 was dissolved in a small amount of ultrapure water, 10 mg of Mal-poly(PEG 77 -co-His) copolymer was dissolved in 10 times the equivalent volume of dichloromethane, mixed and stirred for 1min, added 1% polyvinyl alcohol (PVA) and stirred for 1min, and finally added 10mL PBS and continued to stir for 30min to obtain IL-12 nano-stimulator agent solutions (INPs). The surface Zeta potential, particle size and PDI were detected by DLS, the morphology was observed by TEM and SEM, and the drug loading and encapsulation efficiency were detected by IL-12p70ELISA kit.

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Abstract

The invention discloses a novel targeted drug delivery system of an antibody synthetic bacterium-nano stimulant heterozygote and application of the novel targeted drug delivery system in the field of anti-tumor immunotherapy, and particularly discloses a pH response copolymer, a nano stimulant, an antibody synthetic bacterium and an antibody synthetic bacterium-nano stimulant heterozygote system as well as a preparation method and application of the system.

Description

technical field [0001] The invention belongs to the field of targeted drug delivery systems, and relates to a pH-responsive cytokine nano-stimulator, an antibody synthetic bacterium-nano-stimulator hybrid system, and its application in anti-tumor therapy and the like. Background technique [0002] In recent years, immune checkpoints targeting programmed death receptor 1 (PD-1), programmed death receptor ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have Inhibitory therapy has achieved encouraging results and has become a research hotspot. Blocking the interaction of PD-1 / PD-L1 by immune checkpoint inhibitors and releasing the immunosuppression of the tumor microenvironment is an effective way for anti-tumor immunotherapy. However, due to the disadvantages of traditional immune checkpoint antibody drugs, such as high toxicity, non-renewability, and easy drug resistance, multiple administrations are required in clinical treatment, which severely l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G65/332C08G65/333A61K47/60A61K47/51A61K47/69A61K39/395A61K38/20A61K45/06A61P35/00A61P35/02B82Y5/00B82Y40/00C07K16/28C12N15/70C12N15/74G01N33/53
CPCC08G65/3322C08G65/33317A61K47/60A61K47/51A61K47/6935A61K39/3955A61K38/208A61K45/06A61P35/00A61P35/02B82Y5/00B82Y40/00C07K16/2827C07K16/2818C12N15/70C12N15/74G01N33/53A61K2300/00Y02A50/30
Inventor 蔡林涛廖健洪郑明彬潘宏张保珍黄国俊唐晓帆
Owner SHENZHEN INST OF ADVANCED TECH
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