Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China.
Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Science, Haikou 570100, China.
Acta Biomater. 2023 Mar 1;158:510-524. doi: 10.1016/j.actbio.2022.12.066. Epub 2023 Jan 2.
Cancer vaccines are being explored for enhanced cancer immunotherapy and prophylaxis. Some of their prevailing weaknesses, however, such as complicated preparation, poor biocompatibility, and failure to elicit strong cellular immune responses, have limited their further clinical applications. Here, we reported a multifunctional nanovaccine that was prepared in a quick and simple way. During the self-assembly of metal-phenolic networks (MPNs), the antigen ovalbumin (OVA) and immunoreactive chlorogenic acid (CHA) were simultaneously loaded. Owing to its dual pH and reduction sensitivities, the nanovaccine could deliver antigens into the cytoplasm of dendritic cells (DCs) and facilitate the cross-presentation of antigens. Moreover, the results of in vivo immunization assays demonstrated that the nanovaccine significantly excited the antigen presentation of DCs and provoked a robust cellular immune response with the restrained activation of regulatory T cells (Tregs), by targeting lymph nodes and executing the function of CHA. In vivo antitumor assays indicated that the nanovaccine with good biocompatibility afforded conspicuous cancer treatment and prevention effects. Overall, the nanovaccine presented in this study shows a promise for potentiating cancer immunotherapy by the lymph node-targeted delivery. STATEMENT OF SIGNIFICANCE: Cancer nanovaccines can be used for cancer immunotherapy. However, some existing shortcomings, such as cumbersome preparation, poor biocompatibility, and failure to elicit strong immune responses, limit the clinical application of cancer nanovaccines. This study developed a multifunctional nanovaccine that was readily prepared through the self-assembly of metal-phenolic networks. The nanovaccine with dual pH and reduction sensitivities could efficiently promote the antigen lysosome escape and cross-presentation. In vivo, it efficiently delivered antigen into lymph nodes and provoked strong cellular immune responses, and thus it showed significant cancer immunotherapy and prevention effect.
癌症疫苗正被探索用于增强癌症免疫治疗和预防。然而，它们的一些普遍弱点，如复杂的制备、较差的生物相容性以及未能引发强烈的细胞免疫反应，限制了它们在临床上的进一步应用。在这里，我们报告了一种多功能纳米疫苗，该疫苗的制备方法快速而简单。在金属-酚网络（MPNs）的自组装过程中，同时负载了抗原卵清蛋白（OVA）和免疫反应性绿原酸（CHA）。由于其双重 pH 和还原敏感性，纳米疫苗可以将抗原递送至树突状细胞（DCs）的细胞质中，并促进抗原的交叉呈递。此外，体内免疫接种实验结果表明，纳米疫苗通过靶向淋巴结和执行 CHA 的功能，显著激发 DCs 的抗原呈递，并引发强烈的细胞免疫反应，同时抑制调节性 T 细胞（Tregs）的激活。体内抗肿瘤实验表明，具有良好生物相容性的纳米疫苗具有显著的癌症治疗和预防效果。总之，本研究中提出的纳米疫苗通过淋巴结靶向递送，为增强癌症免疫治疗提供了一种有前途的策略。
