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.

Cell-Membrane-Coated Nanoparticles for Targeted Drug Delivery to the Brain for the Treatment of Neurological Diseases

“…When NDs cause inflammation, WBCs, such as neutrophils, monocytes/macrophages (MMs), and lymphocytes, target the site of inflammation via the interaction between chemokines and chemokine ligands and participate in inflammation progression [ 51 , 52 ]. Among the cell species in which WBC membranes are utilized to fabricate WCMCNPs are mainly neutrophils and MMs ( Table 1 ) [ 27 , 28 , 29 , 33 , 34 , 35 , 36 , 37 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…In addition, macrophages have a more vital ability to move within tissues. Based on these properties, MMs are often used to make drug delivery systems to treat neuroinflammation, brain gliomas, and brain metastases [ 27 , 36 , 37 , 56 ].…”

“…GBM is the most frequent and aggressive malignant type of CNS tumor [ 123 ]. Despite surgical resection and adjuvant therapies, the median survival rate for GBM patients is only 14.6 months due to the specific tumor location and the formidable obstacle of the BBB and the blood–brain tumor barrier (BBTB) [ 37 , 124 , 125 ]. Thus, it is desperately urgent to explore novel drug delivery systems for treating GBM.…”

“…The insertion of NGR peptides into the RBC membrane surface strengthens the ability of drugs to target tumor tissues after crossing the BBB [ 32 ]. Many CMCNPs have shown strong efficiency in crossing the BBB and enhancing the power of drugs to accumulate, specifically in lesions [ 33 , 34 , 35 , 36 , 37 ]. Thus far, various types of cell membranes, such as the red cell membrane, white cell membrane, platelet membrane, cancer cell membrane, and others, have been used to research the fabrication of CMCNPs for treating NDs.…”

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

“…Therefore, the investigators used the PD-1/PD-L1 signaling axis as a starting point to improve the immune microenvironment in glioblastoma. Considering the effect of the blood–brain barrier on drug delivery, Wang et al [ 63 ] proposed using macrophage membranes with good trans-blood–brain barrier ability and tumor homing function for nanodrug delivery. PD-1-MM@PLGA/RAPA consists of a PD-1 overexpressing macrophage membrane wrapped with RAPA-loaded PLGA.…”