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Immune activation-based guanidinylation nano-drug as well as preparation and application thereof

A nano-drug and immune activation technology, applied in the field of medicine, can solve the problems of insignificant therapeutic effect and immune-related adverse reactions of patients, and achieve the effect of reducing toxic side effects and enhancing therapeutic effect

Active Publication Date: 2022-03-15
ZHEJIANG UNIV HANGZHOU GLOBAL SCI & TECH INNOVATION CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the past few decades, chimeric antigen receptor-T cells (CAR-T) and immune checkpoint inhibitors (ICI) have achieved good clinical therapeutic effects, but there are still some problems: CAR- T can cause a "cytokine storm" effect, and patients receiving ICI therapy are often accompanied by severe immune-related adverse reactions
However, compared with chemotherapy, the improvement of treatment effect was not significant

Method used

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  • Immune activation-based guanidinylation nano-drug as well as preparation and application thereof
  • Immune activation-based guanidinylation nano-drug as well as preparation and application thereof
  • Immune activation-based guanidinylation nano-drug as well as preparation and application thereof

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Embodiment 1

[0050] 1. Preparation of nanomedicine

[0051] (1) Dissolve p-aminoacetophenone (4.0g, 29.6mmol), methacryloyl chloride (3.6g, 34.4mmol) and triethylamine (4.0g, 39.6mmol) in dichloromethane (DCM, 100mL) and cooled in an ice bath. The mixture was stirred for 12 hours, then washed successively with saturated sodium bicarbonate solution, hydrochloric acid, distilled water and saturated sodium chloride solution, the solvent was removed by rotary evaporation, N-(4-acetylphenyl)methacrylamide was isolated, and washed with silica gel Purify by chromatography (n-hexane:ethyl acetate=4:1). The final polymerizable monomer after vacuum drying was 2.8 g (yield 46.7%). Its reaction process is:

[0052]

[0053] (2) Polymer PAA is obtained by RAFT polymerization. Get the polymerizable monomer N-(4-acetylphenyl)methacrylamide (0.30g, 1.5mmol) obtained in the previous step, the macromolecular chain transfer agent PETTC-PEG 5k (0.27g, 0.05mmol) and AIBN (6.56mg, 0.04mmol) were dissolv...

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Abstract

The invention discloses a guanidinylated nano-drug based on immune activation as well as preparation and application thereof, and belongs to the technical field of medicines. The nano-drug is a micelle type nano-particle formed by self-assembly of a guanidinylation amphiphilic polymer and a hydrophobic chemotherapeutic drug in water; a hydrophilic segment of the guanidinated amphiphilic polymer is polyethylene glycol, and a hydrophobic segment of the guanidinated amphiphilic polymer is a polymer formed by connecting a pH-responsive hydrazone bond with aminoguanidine. The nano material provided by the invention can release hydrophobic chemotherapeutic drugs in an acidic tumor environment, and tumor cells generate a large number of antigens under the action of the chemotherapeutic drugs. Subsequently, the guanidinylated nanomaterial effectively promotes uptake and cross presentation of antigens by antigen presenting cells such as dendritic cells, and further causes cellular immune response. The nano material realizes combined treatment of chemotherapy and immunotherapy, and greatly enhances the tumor treatment effect.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a guanidinated nano-medicine based on immune activation and its preparation and application. Background technique [0002] Cancer is the second leading cause of death worldwide. Currently, cancer treatment mainly consists of surgical resection, chemotherapy and radiotherapy. Due to the high invasiveness and metastases of tumor cells, surgery generally cannot completely remove the tumor and is often accompanied by postoperative recurrence and other problems. Chemotherapy and radiotherapy have strong side effects due to the lack of selectivity for normal cells and tumor cells. Therefore, there is an urgent need to develop safer and more reliable non-surgical methods to treat tumors. [0003] In recent years, tumor immunotherapy has become a new hot spot. Immunotherapy can precisely recognize and kill tumor cells in an antigen-specific manner by targeting the immune system itsel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/337A61K31/704A61K38/05A61K47/32A61P35/00C08F120/60C08F2/38
CPCA61K9/1075A61K38/05A61K31/704A61K31/337A61K47/32A61P35/00C08F120/60C08F2/38C08F2438/03Y02A50/30
Inventor 唐建斌王睿徐晓丹
Owner ZHEJIANG UNIV HANGZHOU GLOBAL SCI & TECH INNOVATION CENT
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