Abstract

Nowadays, cell membrane-targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane-targeted self-delivery theranostic chimeric peptide CMP-PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real-time therapeutic feedback. Self-assembled CMP-PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP-PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)-carboxyfluorescein (FAM) and 4-(dimethylaminoazo)-benzene-4-carboxylic acid (Dabcyl). More importantly, CMP-PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP-PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp-Glu-Val-Asp (DEVD) is subsequently cleaved by activated caspase-3 and activated caspase-7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase-3 in vitro and in vivo to feedback real-time PDT therapeutic efficacy. In general, a novel cell membrane-targeted self-delivery theranostic chimeric peptide offers new promise for effective imaging-guided PDT.

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