School of Medicine, South China University of Technology, Guangzhou 510006, China.
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, China.
Nano Lett. 2023 Mar 8;23(5):1904-1913. doi: 10.1021/acs.nanolett.2c04970. Epub 2023 Feb 21.
Cancer vaccines have received tremendous attention in cancer immunotherapy due to their capability to induce a tumor-specific immune response. However, their effectiveness is compromised by the insufficient spatiotemporal delivery of antigens and adjuvants in the subcellular level to induce a robust CD8 T cell response. Herein, a cancer nanovaccine G5-pBA/OVA@Mn is prepared through multiple interactions of manganese ions (Mn), benzoic acid (BA)-modified fifth generation polyamidoamine (G5-PAMAM) dendrimer, and the model protein antigen ovalbumin (OVA). In the nanovaccine, Mn not only exerts a structural function to assist OVA loading as well as its endosomal escape, but works as an adjuvant of stimulator of interferon genes (STING) pathway. These collaboratively facilitate the orchestrated codelivery of OVA antigen and Mn into cell cytoplasm. Vaccination with G5-pBA/OVA@Mn not only shows a prophylactic effect, but also significantly inhibits growth against B16-OVA tumors, indicating its great potential for cancer immunotherapy.
癌症疫苗在癌症免疫疗法中受到了极大的关注，因为它们能够诱导肿瘤特异性免疫反应。然而，由于抗原和佐剂在亚细胞水平上的时空传递不足，导致其有效性受到了限制，无法诱导强烈的 CD8 T 细胞反应。在此，通过锰离子（Mn）、苯甲酸（BA）修饰的第五代聚酰胺-胺（G5-PAMAM）树枝状大分子和模型蛋白抗原卵清蛋白（OVA）的多种相互作用，制备了一种癌症纳米疫苗 G5-pBA/OVA@Mn。在纳米疫苗中，Mn 不仅发挥结构功能来协助 OVA 的装载及其内体逃逸，还作为干扰素基因刺激物（STING）途径的佐剂。这些协同作用促进了 OVA 抗原和 Mn 的协调共递送至细胞质。用 G5-pBA/OVA@Mn 进行疫苗接种不仅显示出预防作用，而且还显著抑制了 B16-OVA 肿瘤的生长，表明其在癌症免疫治疗中有很大的潜力。
