首页|Artificial Water Channel Promoting Depolymerization of Actin Filaments to Trigger Cancer Cell Apoptosis

Artificial Water Channel Promoting Depolymerization of Actin Filaments to Trigger Cancer Cell Apoptosis

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Actin filaments play important physiological functions,which have become potential targets of antitumor drugs.Using chemicals to intervene their polymerization-depolymerization dynamics would generate new strategies for designing antitumor drugs.In this re-port,an artificial water channel appending acetazolamide moiety,a ligand that can selectively bind to carbonic anhydrase Ⅸ,has been prepared.We demonstrated that this conjugate can target colorectal cancer cells overexpressing carbonic anhydrase Ⅸ and trigger the depolymerization of actin filaments of the cancer cells by selectively mediating water transmembrane transport.Moreo-ver,the conjugate-promoted actin depolymerization led to tumor cell apoptosis and its high antitumor activity in vitro and in vivo against colorectal cancer.The method described herein represents a new and general strategy for designing antitumor drugs by us-ing artificial channel-mediated selective water transport to promote actin depolymerization.

Artificial water channelActin depolymerizationCell apoptosisNanostructuresMolecular recognitionSupramolecular chemistry

Lei Zhang、Yin-Gui Cao、Ting Fan、Jiatong Zhao、Yong-Hong Fu、Qi Xiao、Zhan-Ting Li、Yunfeng Wang、Bo Xiao、Jun-Li Hou

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Department of Chemistry,Fudan University,220 Handan Road,Shanghai 200433,China

State Key Laboratory of Silkworm Genome Biology,College of Sericulture,Textile,and Biomass Sciences Institution,Southwest University,Chongqing 400715,China

ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital,Fudan University,Shanghai 200031

Fudan International School,325 Guoquan Road,Shanghai 200433,China

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National Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)Science and Technology Commission of Shanghai Municipality(STCSM)

219710462192100322JC1403700

2024

10.1002/cjoc.202300736

中国化学(英文版)
中国化学会 上海有机化学研究所

中国化学(英文版)

CSTPCD
影响因子：0.848
ISSN：1001-604X
年,卷(期)：2024.42(12)