Posttraumatic osteoarthritis(PTOA)patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective.Early PTOA is characterized by overexpressed matrix metalloprotease 13(...Posttraumatic osteoarthritis(PTOA)patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective.Early PTOA is characterized by overexpressed matrix metalloprotease 13(MMP13).Herein,we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable,cyanine 5(Cy5)-containing PEG,black hole quencher-3(BHQ3),and cRGD ligands and loaded with siRNA silencing MMP13(siM13),namely ERMs@siM13.ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell,causing cRGD exposure.Accordingly,the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surfaceαvβ3 integrin,increasing intracellular siM13 delivery for on-demand MMP13 downregulation.Meanwhile,the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle,precisely reflecting the diseased cartilage state.In particular,the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity,enabling the physicians to adjust the therapeutic regimen.Finally,in the murine PTOA model,ERMs@siM13 could diagnose the early-stage PTOA,perform timely interventions,and monitor the OA progression level during treatment through a real-time detection of MMP13.Therefore,ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.展开更多
The generation of methylsufonyl-containing thioflavones through a radical relay reaction of methylthiolated phenylalkynones and potassium metabisulfite in the presence of a catalytic amount of sodium methylsulfinate a...The generation of methylsufonyl-containing thioflavones through a radical relay reaction of methylthiolated phenylalkynones and potassium metabisulfite in the presence of a catalytic amount of sodium methylsulfinate as an initiator under photoinduced conditions is developed.This photocatalytic reaction proceeds smoothly with good functional group tolerance under visible light irradiation.Preliminary mechanistic investigations indicate that this reaction occurs through a radical relay pathway.展开更多
基金supported by Integrated Project of Major Research Plan of National Natural Science Foundation of China (92249303)National Natural Science Foundation of China (82230071,82172098,82371603,82102217,81872428,and 81703010)+7 种基金the Shanghai Rising Star Program (21QA1412000)Shanghai Hospital Development Center (SHDC2023CRT013)Shanghai Committee of Science and Technology (23141900600,Laboratory Animal Research Project)Shanghai Baoshan District Medical Health Project (21-E-14)the Construction of Key Medical Disciplines of Baoshan District of Shanghai (BSZK-2023-Z07)the Shanghai Municipal Natural Science Foundation (23ZR1463300)Postdoctoral Fellowship Program of CPSF (GZB20230397)General Funding for China Postdoctoral Science Foundation (2023M732179).
文摘Posttraumatic osteoarthritis(PTOA)patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective.Early PTOA is characterized by overexpressed matrix metalloprotease 13(MMP13).Herein,we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable,cyanine 5(Cy5)-containing PEG,black hole quencher-3(BHQ3),and cRGD ligands and loaded with siRNA silencing MMP13(siM13),namely ERMs@siM13.ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell,causing cRGD exposure.Accordingly,the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surfaceαvβ3 integrin,increasing intracellular siM13 delivery for on-demand MMP13 downregulation.Meanwhile,the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle,precisely reflecting the diseased cartilage state.In particular,the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity,enabling the physicians to adjust the therapeutic regimen.Finally,in the murine PTOA model,ERMs@siM13 could diagnose the early-stage PTOA,perform timely interventions,and monitor the OA progression level during treatment through a real-time detection of MMP13.Therefore,ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.
基金Financial support from the National Natural Science Foundation of China(No.21901178)the Natural Science Foundation of Zhejiang Province(LY21B020002)+1 种基金the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01005)the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(2020ZD04)is gratefully acknowledged.
文摘The generation of methylsufonyl-containing thioflavones through a radical relay reaction of methylthiolated phenylalkynones and potassium metabisulfite in the presence of a catalytic amount of sodium methylsulfinate as an initiator under photoinduced conditions is developed.This photocatalytic reaction proceeds smoothly with good functional group tolerance under visible light irradiation.Preliminary mechanistic investigations indicate that this reaction occurs through a radical relay pathway.
