Biomimetic Gold Nanostructure with a Virus-like Topological Surface for Enhanced Antigen Cross-Presentation and Antitumor Immune Response.
Biomimetic Gold Nanostructure with a Virus-like Topological Surface for Enhanced Antigen Cross-Presentation and Antitumor Immune Response.
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DOI：
10.1021/acsami.2c21028
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发表时间：
2023-03
影响因子：
9.5
通讯作者：
Zhenyu Wang;Tingting You;Chengyuan Cai;Qianyi Su;Jinmei Cheng;Jisheng Xiao;Xiaopin Duan
中科院分区：
文献类型：
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作者：
Zhenyu Wang;Tingting You;Chengyuan Cai;Qianyi Su;Jinmei Cheng;Jisheng Xiao;Xiaopin Duan
树突状细胞（DC）对抗原的内化是疫苗激活免疫反应的最初关键步骤；然而，将抗原系统性递送至树突状细胞中受到各种技术挑战的阻碍。在这里，我们发现，病毒样金纳米结构（AuNV）由于其仿生拓扑形态，可以有效地与DCs结合并被DCs内化，从而显着促进DCs的成熟和模型抗原卵清蛋白（OVA）的交叉提呈。体内实验表明，AuNV 有效地将 OVA 递送至引流淋巴结，并显着抑制 MC38-OVA 肿瘤的生长，使肿瘤体积减少约 80%。机制研究表明，AuNV-OVA 疫苗可显着提高淋巴结和肿瘤中 DC 成熟率、OVA 呈递以及 CD4+ 和 CD8+ T 淋巴细胞群，并显着减少脾脏中骨髓源性抑制细胞和调节性 T 细胞群。良好的生物相容性、强佐剂活性、增强的 DC 摄取和改善的 T 细胞活化使 AuNV 成为疫苗开发中有前途的抗原递送平台。
The internalization of antigens by dendritic cells (DCs) is the initial critical step for vaccines to activate the immune response; however, the systemic delivery of antigens into DCs is hampered by various technical challenges. Here we show that a virus-like gold nanostructure (AuNV) can effectively bind to and be internalized by DCs due to its biomimetic topological morphology, thereby significantly promoting the maturation of DCs and the cross-presentation of the model antigen ovalbumin (OVA). In vivo experiments demonstrate that AuNV efficiently delivers OVA to draining lymph nodes and significantly inhibits the growth of MC38-OVA tumors, generating a ∼80% decrease in tumor volume. Mechanistic studies reveal that the AuNV-OVA vaccine induces a remarkable increase in the rate of maturation of DCs, OVA presentation, and CD4+ and CD8+ T lymphocyte populations in both lymph node and tumor and an obvious decrease in myeloid-derived suppressor cells and regulatory T cell populations in spleen. The good biocompatibility, strong adjuvant activity, enhanced uptake of DCs, and improved T cell activation make AuNV a promising antigen delivery platform for vaccine development.