Mitochondrial H_(2)S_(n)-Mediated Anti-Inflammatory Theranostics  

作　　者：Won Young Kim Miae Won Seyoung Koo Xingcai Zhang Jong Seung Kim 

机构地区：[1]Department of Chemistry,Korea University,Seoul 02841,Korea [2]John A.Paulson School of Engineering and Applied Sciences,Harvard University,Cambridge,MA 02138,USA [3]School of Engineering,Massachusetts Institute of Technology,Cambridge,MA 02139,USA

出　　处：《Nano-Micro Letters》2021年第12期1-13,共13页纳微快报（英文版）

基　　金：supported by the National Research Foundation of Korea(CRI project no.2018R1A3B1052702 and 2019M3E5D1A01068998,J.S.K.);Basic Science Research Program(2020R1A6A3A01100551,M.W.and 2020R1A6A3A01100558,S.K.)funded by the Ministry of Education;Korea University Grant。

摘　　要：The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.

关 键 词：THERANOSTICS ANTI-INFLAMMATION MITOCHONDRIA Hydrogen polysulfides 

分 类 号：R943[医药卫生—药剂学]