Biomimetic hybrid membranes-camouflaged biosynthesized melanin nanoparticles for efficient cancer photothermal-immunotherapy

Abstract Biomimetic membranes-camouflaged nanomedicines show promising potential in cancer therapy. Herein, we developed biomimetic hybrid membranes-camouflaged biosynthesized melanin nanoparticles, termed MBM-PM, by co-extruding near-infrared (NIR) light-absorbing melanin nanoparticles naturally enveloped in bacterial outer membranes (MBM) with programmed cell death protein 1 (PD-1)-expressing mammalian cell membrane nanovesicles (PM), for efficient cancer photothermal-immunotherapy. The melanin core within the outer membrane vesicles (OMV) generates a photothermal effect, inducing thermal stress to directly kill cancer cells and triggering immunogenic cell death (ICD), which enhances antitumor immunity. Furthermore, the pathogen-associated molecular patterns (PAMPs) present in the bacterial membrane component of MBMs stimulate a robust antitumor immune response. The PM components not only confer cancer cell-targeting capability but also block the PD-1/programmed death-ligand 1 (PD-L1) interaction, further enhancing immune activation. Our studies demonstrate that the MBM-PM nanoplatform can effectively eradicate primary tumors and significantly inhibit distant tumors and lung metastasis, offering a promising biosynthesized nanoplatform for cancer photothermal-immunotherapy.