4.4 Article

H2S-Responsive Small-Molecule Nanocarriers for Drug Delivery to Colorectal Tumors

期刊

ADVANCED THERAPEUTICS
卷 5, 期 9, 页码 -

出版社

WILEY
DOI: 10.1002/adtp.202200044

关键词

cancer therapy; triggered drug release; hydrogen sulfide; nanocarrier; self assembly; three-legged molecule

资金

  1. National Natural Science Foundation of China [81803469]

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This study develops a H2S-responsive nanocarrier based on self-assembly, which can be used for controlled drug release in cancer therapy. The results show that the nanocarrier exhibits efficient H2S-responsive drug release in colon cancer cells and effectively inhibits tumor growth in animal models.
Hydrogen sulfide (H2S), a gaseous signaling molecule, is excessively produced in disease lesions like lung tumors and colorectal tumors. H2S is used as a trigger for stimuli-responsive drug delivery in cancer therapies, which enables controlled release of chemotherapeutics and improves their biocompatibility and efficacy. Herein, a H2S-responsive small-molecule nanocarrier is developed based on the self-assembly of a trigonal molecule, tris(azido benzyl)-tri(2-aminoethyl) amine (ATAEA). ATAEA with three H2S-responsive azido benzyl groups can self-assemble into nanocarriers (ATNPs) and encapsulate hydrophobic doxorubicin (DOX) to form drug-loaded nanoparticles (DOX/ATNPs). H2S induces the reduction of azido benzyl group and 1,6-elimination, which results in the dissociation of the ATAEA molecules and the nanoparticles. In HCT116 colon cancer cells, efficient H2S-responsive DOX release from DOX/ATNPs is observed. In vivo administration of DOX/ATNPs in colon tumor-bearing mice leads to higher drug accumulation in tumors and evident tumor growth inhibition, in comparison with non-responsive nanoparticles. This work provides a new strategy to develop H2S-responsive drug delivery systems for precise drug delivery to H2S-enriched disease lesions.

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