Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
ACS Nano. 2024 Jan 30;18(4):3349-3361. doi: 10.1021/acsnano.3c10174. Epub 2024 Jan 17.
Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate--butyl methacrylate--2-(azepan-1-yl)ethyl methacrylate (PEGMA--BMA--C7AMA) graft copolymers with designed proportions of different components to regulate their properties. Among these polymers, C-25, with a C7AMA:BMA ratio at 1.5:1 and PEG wt % of 25%, was screened as the most effective nanovaccine carrier with enhanced ability to induce mouse bone marrow-derived dendritic cell (BMDC) maturation. Additionally, RNA-sequencing (RNA-Seq) analysis revealed that C-25 could activate dendritic cells (DCs) through multisignaling pathways to trigger potent immune effects. Then, the screened C-25 was used to encapsulate the model peptide antigen, OVA, to form nanovaccine C-25/OVA. It was found that the C-25/OVA nanovaccine could effectively facilitate DC maturation and antigen cross-presentation without any other additional adjuvant and exhibited excellent prophylactic efficacy in the B16F10-OVA tumor model. Moreover, in combination with antiprogrammed cell death protein-ligand 1 (anti-PD-L1), the C-25/OVA nanovaccine could significantly delay the growth of pre-existing tumors. Therefore, this work developed a minimalist nanovaccine with a simple formulation and high efficiency in activating tumor-specific immune responses, showing great potential for further application in cancer immunotherapy.
具有诱导肿瘤特异性免疫应答能力的癌症疫苗在癌症免疫治疗中引起了极大的关注。有效的癌症疫苗的一个关键挑战是抗原和佐剂的时空共递呈。在此,我们合成了一个包含九个聚乙二醇甲基醚甲基丙烯酸酯-丁基甲基丙烯酸酯-2-(氮杂环庚烷-1-基)乙基甲基丙烯酸酯(PEGMA-BMA-C7AMA)接枝共聚物的嵌段共聚物库,其中不同成分的比例设计用于调节其性质。在这些聚合物中,C-25 具有 1.5:1 的 C7AMA:BMA 比和 25%的 PEGwt%,被筛选为最有效的纳米疫苗载体,具有增强诱导小鼠骨髓来源树突状细胞(BMDC)成熟的能力。此外,RNA 测序(RNA-Seq)分析表明,C-25 可以通过多信号通路激活树突状细胞(DCs),引发强大的免疫效应。然后,筛选出的 C-25 被用于包裹模型肽抗原 OVA,形成纳米疫苗 C-25/OVA。结果发现,C-25/OVA 纳米疫苗可以有效地促进 DC 成熟和抗原交叉呈递,而无需任何其他额外的佐剂,并在 B16F10-OVA 肿瘤模型中表现出优异的预防功效。此外,与抗程序化细胞死亡蛋白配体 1(抗 PD-L1)联合使用时,C-25/OVA 纳米疫苗可以显著延缓已存在肿瘤的生长。因此,本工作开发了一种具有简单配方和高效激活肿瘤特异性免疫应答能力的极简纳米疫苗,在癌症免疫治疗中具有很大的应用潜力。
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