Cell Membrane Camouflaged Metal Oxide-Black Phosphorus Biomimetic Nanocomplex Enhances Photo-chemo-dynamic Ferroptosis.

Abstract

Despite the availability of various treatment options, the inherent complexity of tumors significantly impairs therapeutic efficacy. Recently, combination treatments exhibited great anticancer potential due to low cross-resistance and good therapeutic additivity. Herein, a photoactive metal oxide-black phosphorus biomimetic nanocomplex (photophage) is developed for improving the antitumor combination of ferroptosis and photodynamic therapy (PDT). The photophage is composed of M1 macrophage membrane camouflaged MnO2 and Fe3O4 nanoparticles anchored black phosphorus nanosheets (BPNs), which together trigger a synergistic antitumor action. Fe3O4 acts as an iron source to activate Fenton-reaction-dependent ferroptosis, which can be further strengthened by BPN-mediated PDT. Besides the original antitumor effects, PDT also generates reactive oxygen species to enhance lipid peroxidation and glutathione depletion, which in turn reinforce ferroptosis and PDT efficacy. Importantly, MnO2 can in situ generate oxygen to relieve tumor hypoxia and consequently leverage cell behaviors to improve therapeutic responses. Particularly, M1 macrophage membrane modification endows the photophage with good tumor targeting capability and tumor penetration, which promote synergistic ferroptosis and PDT to destroy tumors while reducing systemic side effects, resulting in the prolonged survival of tumor-bearing mice. Therefore, we present a biomimetic nanoplatform for overcoming tumor barriers and advancing tumor-targeted treatment.