一种新型的氟聚合物作为蛋白质传递载体，并具有强效的肿瘤免疫治疗辅助效果。
A novel fluoropolymer as a protein delivery vector with robust adjuvant effect for cancer immunotherapy.
发表日期：2023 Sep 08
作者：
Yu-Rong Zhan, Xi He, Zhi-Ying Huang, Ping Chen, Miao-Miao Tian, Guo-Hong Li, Xiao-Qi Yu, Xiang-Rong Song, Ji Zhang
来源：
CYTOKINE & GROWTH FACTOR REVIEWS
摘要：
由于蛋白质基纳米疫苗的免疫原性不足，导致其治疗效果低效。在此，我们通过开环聚合反应制备了一种新型的氟聚合物（PF），并构建了一种基于氟聚合物的肿瘤免疫疫苗。由于存在氟烷基链，PF不仅在肿瘤抗原输送中发挥了关键作用，还展现出显著的佐剂效应，增强了纳米疫苗的免疫原性。通过将PF与模型抗原卵清蛋白（OVA）混合形成的纳米疫苗增强了树突状细胞（DCs）对抗原蛋白的摄取，并促进了DCs的成熟和抗原呈递。与游离OVA相比，PF/OVA在癌前预防和肿瘤治疗方面表现出更好的效果。此外，接种PF/OVA的小鼠的淋巴结和肿瘤中CD4+ T细胞和CD8+ T细胞的比例显著增加。此外，接种PF/OVA的小鼠血清中关键的抗肿瘤细胞因子（TNF-α和IFN-γ）水平明显增加。我们的研究表明，作为蛋白质载体和佐剂的氟聚合物PF具有很大的潜力，可用于开发具有强大免疫原性的纳米疫苗。
The inefficient treatment using protein-based nanovaccines is largely attributed to their inadequate immunogenicity. Herein, we developed a novel fluoropolymer (PF) via ring-opening polymerization and constructed a fluoropolymer-based nanovaccine for tumor immunotherapy. Due to the existence of fluoroalkyl chains, PF not only played a crucial role in tumor antigen delivery but also exhibited a remarkable adjuvant effect in enhancing the immunogenicity of nanovaccines. The nanovaccines formed by mixing PF with a model antigen ovalbumin (OVA) enhanced the uptake of antigen proteins by dendritic cells (DCs) and promoted the maturation and antigen presentation of DCs. Compared with free OVA, PF/OVA showed better efficacy in both pre-cancer prevention and tumor treatment. Furthermore, the proportion of CD4+ T and CD8+ T cells was significantly increased in lymph nodes and tumors of mice immunized with PF/OVA. Additionally, there was a great enhancement in the levels of key anti-tumor cytokines (TNF-α and IFN-γ) in the serum of the PF/OVA immunized mice. Our research has shown that fluoropolymer PF applied as a protein vector and adjuvant has great potential for the development of nanovaccines with robust immunogenicity.