Enhanced Antiglioma Effect by a Vitamin D3-Inserted Lipid Hybrid Neutrophil Membrane Biomimetic Multimodal Nanoplatform

Abstract

Glioblastoma, the most prevalent malignant brain tumor, is a lethal threat to human health, with aggressive and infiltrative growth characteristics that compromise the clinical treatment. Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO₂-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO₂) which were coated with a vitamin D₃-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO₂-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8⁺T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a "cold" tumor to a "hot" tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.

Keywords: biomimetic; cGAS-STING signaling pathway; drug delivery; glioblastoma; multimodal immunotherapy.