Erythrocyte membrane-camouflaged Prussian blue nanocomplexes for combinational therapy of triple-negative breast cancer

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.