Biomimetic neutrophil and macrophage dual membrane-coated nanoplatform with orchestrated tumor-microenvironment responsive capability promotes therapeutic efficacy against glioma

Malignant glioma is a significant problem in public health worldwide, due to high infiltrative glioma growth, chemotherapeutic tumor resistance, and formidable obstacle of blood–brain barrier (BBB). Therapeutic drug delivery platforms that can overcome the BBB hurdle and target glioma are urgently needed. Encouraged by the involvement of immune cells in inflammatory response, and their important role in regulating glioma maintenance and progression, we introduce an effective approach based on neutrophil-macrophage hybrid membrane coating nanotechnology for glioma treatment. By covering a rapamycin (RAPA)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle with neutrophil and macrophage membranes (NMm), this biomimetic nanoparticle (NMm-PLGA/RAPA) possesses spontaneous BBB penetrating, and inherently combines the stimuli-homing responsiveness of macrophage with the inflammatory chemotaxis of neutrophils. An in vivo brain inflammatory study confirms that the NMm-PLGA/RAPA can efficiently transmigrate across BBB, respond to inflammatory stimuli, and specifically accumulate within the inflammatory site. On injection of NMm-PLGA/RAPA into a mouse glioma model, the NMm-PLGA/RAPA is found to target the brain tumor, and is capable of eliminating glioma cells and inducing durable tumor regression. Our neutrophil and macrophage membrane-coated nanoplatform presents a viable and efficient drug delivery system able to increase therapeutic efficacy for glioma and possibly other malignant tumors.