A Single‐Component Dual Donor Enables Ultrasound‐Triggered Co‐release of Carbon Monoxide and Hydrogen Sulfide

作者：Mengdan Zhang, Jian Cheng, Zhiqiang Shen, Paiyu Lin, Shenggang Ding, Jinming Hu · 发表于：Angewandte Chemie International Edition · 年份：2023 · DOI：10.1002/anie.202314563 · 被引用次数：57 · 研究领域：Heme Oxygenase-1 and Carbon Monoxide、Sulfur Compounds in Biology、Nanoplatforms for cancer theranostics

Abstract The development of dual gasotransmitter donors can not only provide robust tools to investigate their subtle interplay under pathophysiological conditions but also optimize therapeutic efficacy. While conventional strategies are heavily dependent on multicomponent donors, we herein report an ultrasound‐responsive water‐soluble copolymer ( PSHF ) capable of releasing carbon monoxide (CO) and hydrogen sulfide (H 2 S) based on single‐component sulfur‐substituted 3‐hydroxyflavone (SHF) derivatives. Interestingly, sulfur substitution can not only greatly improve the ultrasound sensitivity but also enable the co‐release of CO/H 2 S under mild ultrasound irradiation. The co‐release of CO/H 2 S gasotransmitters exerts a bactericidal effect against Staphylococcus aureus and demonstrates anti‐inflammatory activity in lipopolysaccharide‐challenged macrophages. Moreover, the excellent tissue penetration of ultrasound irradiation enables the local release of CO/H 2 S in the joints of septic arthritis rats, exhibiting superior therapeutic efficacy without the need for any antibiotics.