Biomimetic carbon nanopolymers ANM-NPs act on mannose receptors and complement receptors to promote tumor antigen presentation

仿生碳纳米聚合物ANM-NPs作用于甘露糖受体和补体受体,促进肿瘤抗原呈递

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作者:Zhuangzhuang Feng # ,Xinxiu Shi # ,Zhiyang Li # ,Minming Lou # ,Bijia Cui ,Mengzhan Chen ,Lei Zhang ,Yujie Sun ,Heng Zhang ,Yi-Nan Li ,Huijuan Liu ,Tao Sun

Abstract

Background: Enhancing immunogenicity and antigen-presentation efficiency is critical for tumor vaccine development. While yeast-surface glycoprotein side chains can improve antigen presentation, their ability to deliver tumor antigens remains limited. Methods: The composite carbon nanopolymers (Asparagine-N-acetylglucosamine-Mannose derived carbon nanopolymers, ANM-NPs) mimicking yeast-surface glycans side chains were prepared using asparagine, N-acetylglucosamine and mannose as precursors via microwave-assisted synthesis method. Combined with whole-cell tumor antigen (T-Ag), the vaccine ANM-NPs@T-Ag was prepared. The expression levels of major histocompatibility complex-II, CD80, and CD86 were analyzed by flow cytometry to evaluate the enhancement of antigen presentation. The antitumor efficacy of ANM-NPs@T-Ag was assessed by H22-LUC and B16-F10-LUC tumor-bearing models. Results: ANM-NPs have an average particle size of approximately 21.69 nm and exhibit good stability. Compared with traditional aluminum adjuvants, ANM-NPs demonstrate superior efficacy in promoting antigen presentation and immune activation. ANM-NPs effectively stimulated innate immunity, facilitated immune cell infiltration, and enhanced adaptive immune responses. The vaccine ANM-NPs@T-Ag targeted dendritic cells via mannose receptors, activating the lectin pathway, improving complement opsonization, and enhancing antigen presentation. ANM-NPs@T-Ag stimulated cellular/humoral immunity, increased tumor-specific IgG, and inhibited tumor growth. ANM-NPs@T-Ag also enhanced the antitumor effect of α-PD-1 (programmed cell death protein-1). Conclusion: These findings demonstrate that ANM-NPs can serve as a potential vaccine adjuvant, and ANM-NPs@T-Ag represents a promising tumor vaccine candidate.Cite Now.

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