Abstract
Drug resistance is an important reason to the treatment failure of cancer chemotherapy. In this paper, an amphiphilic tumor-targeting chimeric peptide-based drug self-delivery system (DSDS) was designed to overcome drug resistance by synergistic chemo-photodynamic therapy. Doxorubicin (Dox) was encapsulated into the micelles formed by the self-assembly of protoporphyrin IX (PpIX) derivated amphiphilic chimeric peptides (PpIX-PEG8-PEG8-RGDS) with high loading capacities of 25.85% for DOX and 29.49% for PpIX. The RGDS peptide moiety promoted the cell internalization of micelles by αυβ3 integrin-overexpressed cancer cells. Upon given 630 nm light irradiation, cytotoxic reactive oxygen species (ROS) were generated from PpIX to destroy the lysosomes and help release the micelles, which further underwent efficient therapeutic effect to MCF-7/ADR cells. The micelles undergo photodynamic therapy while slowly release DOX in lysosomes, preventing DOX from being pumped out the cell by P-glycoprotein. The nanomicellar drug self-delivery system proposed in this work exhibited significantly synergistic chemo-photodynamic therapy and provided a new platform for the therapy of drug resistant tumor cells.
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