Engineered Macrophage-Membrane-Coated Nanoparticles with Enhanced PD-1 Expression Induce Immunomodulation for a Synergistic and Targeted Antiglioblastoma Activity

Abstract

Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood–brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression (PD-1-MM@PLGA/RAPA). Using both in vitro and in vivo GBM models, we demonstrate that PD-1-MM@PLGA/RAPA can efficiently traverse across the BBB in response to the tumor microenvironment (TME) recruitment with nanoparticles accumulating at the tumor site. Furthermore, we show a boosted immune response as a result of enhancing CD8 + cytotoxic T-lymphocyte (CTL) infiltration. Together we provide a new nanoplatform for enhancing ICB in combination with conventional chemotherapy for GBM and many other cancers.