Enhanced Antiglioma Effect by a Vitamin D3-Inserted Lipid Hybrid Neutrophil Membrane Biomimetic Multimodal Nanoplatform
Weichong He, Wei Lv, Linfeng Liu, Yue Gong, Kefan Song, Jiangna Xu, Wei Zhao, Shengnan Li, Zhiyi Min, Qinhua Chen, Jiaqing Yin, Yuqin Chen, Hufeng Fang, Hongliang Xin, Xiangming Fang
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@MnO 2 -DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO 2 ) which were coated with a vitamin D 3 -inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO 2 -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.