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...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.展开更多
H_(2)S is well-known as a colorless,acidic gas,with a notoriously rotten-egg smell.It was recently revealed that H_(2)S is also an endogenous signaling molecule that has important biological functions,however,most of ...H_(2)S is well-known as a colorless,acidic gas,with a notoriously rotten-egg smell.It was recently revealed that H_(2)S is also an endogenous signaling molecule that has important biological functions,however,most of its physiology and pathology remains elusive.Therefore,the enthusiasm for H_(2)S research remains.Fluorescence imaging technology is an important tool for H_(2)S biology research.The development of fluorescence imaging technology has realized the study of H_(2)S in subcellular organelles,facilitated by the development of fluorescent probes.The probes reviewed in this paper were categorized according to their chemical mechanism of sensing and were divided into three groups:H_(2)S reducibility-based probes,H_(2)S nucleophilicity-based probes,and metal sulfide precipitation-based probes.The structure of the probes,their sensing mechanism,and imaging results have been discussed in detail.Moreover,we also introduced some probes for hydrogen polysulfides.展开更多
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 EducationKorea University Grant。
文摘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.
基金supported by China Postdoctoral Science Foundation(Grant No.2019M652053).
文摘H_(2)S is well-known as a colorless,acidic gas,with a notoriously rotten-egg smell.It was recently revealed that H_(2)S is also an endogenous signaling molecule that has important biological functions,however,most of its physiology and pathology remains elusive.Therefore,the enthusiasm for H_(2)S research remains.Fluorescence imaging technology is an important tool for H_(2)S biology research.The development of fluorescence imaging technology has realized the study of H_(2)S in subcellular organelles,facilitated by the development of fluorescent probes.The probes reviewed in this paper were categorized according to their chemical mechanism of sensing and were divided into three groups:H_(2)S reducibility-based probes,H_(2)S nucleophilicity-based probes,and metal sulfide precipitation-based probes.The structure of the probes,their sensing mechanism,and imaging results have been discussed in detail.Moreover,we also introduced some probes for hydrogen polysulfides.
