Virus‐Like Nanotherapeutic for Spatiotemporally Enhancing Antigen Presentation and Cross‐Presentation toward Potential Personalized Immunotherapy

• DOI: 10.1002/adhm.202300921
• Publication Date: 2023-08-02T16:30:07Z
• Authors: Xiaodi Li; Pengfei Yuan; Haiyuan Yang; Xiaoqing Zong; Caiqi Yang; Xinjie Chen; Yuchao Li; Xiaodie Yan; Yaoqi Wen; Tianci Zhu; Qian Zhang; Wei Xue; Jian Dai
• Keywords: Cross-Presentation

One of the major causes immunotherapy resistance is loss histocompatibility complex class I (MHC-I) molecules in tumor cells or downregulation antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) developed via encapsulating nanosized siRNA nanoparticles hybrid membrane comprising personalized cell and universal 293T expressing mutant vesicular stomatitis virus glycoprotein (mVSV-G). Upon intravenous administration, siRNA@HCM accumulates at site provides two potent driving forces for antitumor immunity. First, mVSV-G induces fusion with membranes directly injects siRNAs into cytoplasm, significantly improving intrinsic MHC-I presentation. Moreover, can promote maturation dendritic cells, thereby achieving highly efficient cross-presentation. The results demonstrate that spatiotemporally enhancing cross-presentation achieve satisfactory efficacy excellent biocompatibility. Immune infiltration analysis shows treatment turns cold tumors hot tumors. addition, it promotes therapeutic effect programmed death-1 inhibitor. summary, nanotherapeutics present promising approach to enhance immune response, distinct advantages potential therapy clinical applications.