Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macro-phages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS chal-lenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Automated summary

A biomimetic nanosystem was developed to escape the mononuclear phagocyte system (MPS) and target tumor tissues. The nanoparticles were coated with fibroblast cell membrane expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which reduced macrophage endocytosis and increased tumor cell uptake. Additionally, encapsulated chloroquine (CQ) suppressed macrophage uptake and synergized with TRAIL to induce tumor cell apoptosis.