Abstract

Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC–B16), and RBC–B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC–B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC–B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC–B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC–B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.