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

Author:

Li Xiaodi1,Yuan Pengfei1,Yang Haiyuan1,Zong Xiaoqing1,Yang Caiqi1,Chen Xinjie1,Li Yuchao1,Yan Xiaodie1,Wen Yaoqi1,Zhu Tianci1,Zhang Qian1,Xue Wei1,Dai Jian1ORCID

Affiliation:

1. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes Engineering Technology Research Center of Drug Carrier of Guangdong Department of Biomedical Engineering Jinan University Guangzhou 510632 China

Abstract

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

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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