期刊文献

Mannan-decorated pathogen-like polymeric nanoparticles as nanovaccine carriers for eliciting superior anticancer immunity 收藏

曼南装饰的病原体样聚合物纳米颗粒作为纳米甲烷载体，用于引起上级抗癌免疫力

原文求助发布源

作者

Yudi Xu[a][b][d];Sheng Ma[a][d];Jiayu Zhao[a][c][d];Hongyu Chen[a][c][d];Xinghui Si[a][c][d];Zichao Huang[a][c][d];Zhentao Yu[e];Wantong Song[a][d];Zhaohui Tang[a][c][d];Xuesi Chen[a][c][d]

作者单位

[a]Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, ChinaKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China[b]University of Chinese Academy of Sciences, Beijing, 100039, ChinaUniversity of Chinese Academy of Sciences, Beijing, 100039, China[c]University of Science and Technology of China, Hefei, 230026, ChinaUniversity of Science and Technology of China, Hefei, 230026, China[d]Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, ChinaJilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China[e]Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, ChinaDepartment of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China

发布日期

1 May 2022

DOI

10.1016/j.biomaterials.2022.121489

来源信息

Biomaterials ISSN：0142-9612, 2022年, 284卷

摘要

Using nanotechnology for cancer vaccine design holds great promise because of the intrinsic feature of nanoparticles in being captured by antigen-presenting cells (APCs). However, there are still obstacles in current nanovaccine systems in achieving efficient tumor therapeutic effects, which could partially be attributed to the unsatisfactory vaccine carrier design. Herein, we report a mannan-decorated pathogen-like polymeric nanoparticle as a protein vaccine carrier for eliciting robust anticancer immunity. This nanovaccine was constructed as a core-shell structure with mannan as the shell, polylactic acid-polyethylenimine (PLA-PEI) assembled nanoparticle as the core, and protein antigens and Toll-like receptor 9 (TLR9) agonist CpG absorbed onto the PLA-PEI core via electrostatic interactions. Compared to other hydrophilic materials, mannan decoration could greatly enhance the lymph node draining ability of the nanovaccine and promote the capturing by the CD8⁺ dendritic cells (DCs) in the lymph node, while PLA-PEI as the inner core could enhance antigen endosome escape thus promoting the antigen cross-presentation. In addition, mannan itself as a TLR4 agonist could synergize with CpG for maximally activating the DCs. Excitingly, we observed in several murine tumor models that using this nanovaccine alone could elicit robust immune response in vivo and result in superior anti-tumor effects with 50% of mice completely cured. This study strongly evidenced that mannan decoration and a rationally designed nanovaccine system could be quite robust in tumor vaccine therapy.

摘要译文

使用纳米技术进行癌症疫苗设计具有很大的希望，因为纳米颗粒在被抗原呈递细胞（APC）捕获时具有内在特征。然而，当前纳米霉素系统仍在达到有效的肿瘤治疗作用方面仍然存在障碍，这可能部分归因于疫苗载体设计不令人满意。在本文中，我们报告了一种曼南装饰的病原体样聚合物纳米颗粒作为蛋白质疫苗载体，用于引起健壮的抗癌免疫。该纳米霉素被构建为具有曼南的核心壳结构，作为壳，聚乳酸 - 多甲基亚胺（PLA-PEI）组装的纳米颗粒作为核心，以及蛋白质抗原和Toll-like受体9（TLR9）激动剂在Pla-andist cpg上吸收了Pla-andist cpg PEI芯通过静电相互作用。与其他亲水材料相比，曼南装饰可以极大地增强纳米酮的淋巴结排水能力，并促进CD8 ⁺+ dendritic细胞（DCS）的捕获，而PLA-PEI则作为PLA-PEI作为PLA-PEI内核可以增强抗原内体逃逸，从而促进抗原交叉呈递。此外，曼南本身作为TLR4激动剂可以与CPG协同起来，以最大程度地激活DC。令人兴奋的是，我们在几个鼠肿瘤模型中观察到，单独使用这种纳米酮可以在体内产生强大的免疫反应，并导致抗肿瘤作用出色，而50％的小鼠完全治愈。这项研究强烈证明，曼南装饰和合理设计的纳米酮系统在肿瘤疫苗治疗中可能非常健壮。

Yudi Xu[a][b][d];Sheng Ma[a][d];Jiayu Zhao[a][c][d];Hongyu Chen[a][c][d];Xinghui Si[a][c][d];Zichao Huang[a][c][d];Zhentao Yu[e];Wantong Song[a][d];Zhaohui Tang[a][c][d];Xuesi Chen[a][c][d]. Mannan-decorated pathogen-like polymeric nanoparticles as nanovaccine carriers for eliciting superior anticancer immunity[J]. Biomaterials, 2022,284