Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 25, Issue 47, Pages 7317-7326Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201503262
Keywords
apoptosis imaging; drug release monitors; FRET; prodrugs; theranostics
Categories
Funding
- National Natural Science Foundation of China [51125014, 51233003, 21474077]
- Ministry of Science and Technology of China [2011CB606202]
- Natural Science Foundation of Hubei Province of China [2013CFA003]
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A dual-Forster 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 (v3) 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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