A Dual‐FRET‐Based Versatile Prodrug for Real‐Time Drug Release Monitoring and In Situ Therapeutic Efficacy Evaluation |
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Authors: | Shi‐Ying Li Li‐Han Liu Lei Rong Wen‐Xiu Qiu Hui‐Zhen Jia Bin Li Fei Li Xian‐Zheng Zhang |
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Affiliation: | Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, P. R. China |
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Abstract: | A dual‐Förster resonance energy transfer (FRET)‐based versatile prodrug (V‐prodrug), in which the fluorescence of both 5(6)‐carboxylfluorescein (FAM) and doxorubicin (DOX) can be quenched by 4‐(dimethylaminoazo)benzene‐4‐carboxylic acid (Dabcyl) with high quenching efficiency, is developed in this paper. The V‐prodrug can selectively bind to the αvβ3 integrin overexpressed cancer cells through the Arg‐Gly‐Asp (RGD) targeting moiety. After that, the acid‐mediated DOX release of the V‐prodrug can be real‐time monitored by the increase of the red fluorescence from DOX. Thereafter, DOX‐induced cell apoptosis can also be in situ assessed by the fluorescence recovery of the FAM, due to the caspase‐3‐mediated Asp‐Glu‐Val‐Asp (DEVD) peptide sequence cleavage. This novel prodrug provides a cascaded imaging of real‐time drug release and subsequent cell apoptosis, which enables the in situ detection of the cancer response and the therapeutic efficacy evaluation of the prodrug. |
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Keywords: | apoptosis imaging drug release monitors FRET prodrugs theranostics |
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