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Rapid discovery of drug-introduced multiple organ dysfunction via NIR-Ⅱ fluorescent imaging

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摘要 The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed near-infrared window two(NIR-II)fluorescent bioimaging method that allows for real-time,rapid,and quantitative assessment of multiple organ dysfunctions.Given that existing probes did not fully meet requirements,we synthesized a range of NIR-II hemicyanine dyes(HDs)with varying absorption and emission wavelengths.By modifying these dyes,we achieved high spatial and temporal resolution imaging of the liver,kidneys,stomach,and intestines.This method was further applied to investigate disorders induced by cisplatin,a drug known to cause gastric emptying issues along with liver and kidney injuries.By monitoring the metabolic rate of the dyes in these organs,we accurately quantified multi-organ dysfunction,which was also confirmed by gold-standard pathological analysis.Additionally,we evaluated the effects of five aristolochic acids(AAs)on multiple organ dysfunction.For the first time,we identified that AA-I and AA-II could cause gastric emptying disorders,which was further validated through transcriptomics analysis.Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction,which may significantly enhance the evaluation of drug side effects.
出处 《Acta Pharmaceutica Sinica B》 2025年第8期4285-4299,共15页 药学学报(英文版)
基金 supported by the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China) the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB1040000,China) the National Natural Science Foundation of China(Nos.32141005 and 82071976,China) the National Key Research and Development Program of China(No.2023YFA1800804) Science and Technology Innovation Key R&D Program of Chongqing(No.CSTB2023TIAD-STX0006,China) the National Science and Technology Innovation 2030 Major Project of China(No.2021ZD0203900).
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