Abstract

Although combined photodynamic/photothermal therapy (PDT/PTT) has been used for cancer theranostics recently, their therapeutic efficacy has been compromised by the low O2 partial pressure and high concentration of GSH in the tumor microenvironment (TME). Thus, the construction of intelligent TME-responsive nanocomplexes is a powerful strategy for addressing the above issues. In this study, MnO2-coated Prussian blue nanocomplexes (PM NPs) were designed as O2 suppliers and GSH depletion agents to reprogram the TME. Subsequently, tumor-targeting peptide (RGD)-modified erythrocyte membrane vesicles loaded with photosensitizer (Ce6) were used to camouflage PM NPs (PMRCR NPs). Importantly, the prepared PMRCR NPs exhibited excellent photothermal performance with a photothermal conversion efficiency of 44.9%. Moreover, the in vitro PDT/PTT was enhanced, by which the cell viability was reduced to 21.4%, which is lower than the 55.6% (PDT) and 66.7% (PTT) of PMRCR NPs with a single laser treatment. By modeling 4T1 tumor-bearing mice, the combined PDT/PTT of PMRCR NPs greatly inhibited tumor growth, and after 20 days, a tumor inhibition rate of 92.9% was achieved. This work provides a promising strategy by developing TME-reprogrammed multifunctional nanocomplexes to enhance PDT/PTT antitumor efficacy.