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

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.