Wang Ning, Yang Ying, Wang Xiaoli, Tian Xinxin, Qin Wenjuan, Wang Xiaoxiao, Liang Jiayi, Zhang Hailing, Leng Xigang
Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
ACS Biomater Sci Eng. 2019 May 13;5(5):2330-2342. doi: 10.1021/acsbiomaterials.9b00359. Epub 2019 Apr 23.
This study aimed to investigate the efficacy of polydopamine nanoparticles (Pdop-NPs) as a subcutaneous antigen delivery vehicle in antitumor therapy. The nanoparticles were prepared by self-polymerization of dopamine in an aerobic and weak alkaline solution, and the tumor model antigen-ovalbumin (OVA) was grafted onto the nanoparticles to form OVA@Pdop nanoparticles (OVA@Pdop-NPs). The particle size of OVA@Pdop-NPs was 232.8 nm with a zeta potential of -23.4 mV, and the loading capacity of OVA protein was 754 μg mg. OVA@Pdop-NPs were essentially noncytotoxic and even demonstrated a slightly viability effect on bone-marrow-derived dendritic cells (BMDCs). As compared to free OVA, OVA@Pdop-NPs exhibited higher cellular uptake and were easier to migrate to lymph nodes in vivo. Both in vitro and in vivo experiments showed that OVA@Pdop-NPs promoted the maturation of DCs with up-regulated expression of major histocompatibility complex (MHC), costimulatory molecules, and cytokines. When used to treat the mice bearing OVA-MC38 colon tumor, OVA@Pdop-NPs could effectively activate OVA-specific cytotoxic CD8 T cells and induce the production of memory CD4 and CD8 T cells and thus led to significantly suppressed tumor growth. All the preliminary data demonstrated the application potential of OVA@Pdop-NPs as a vaccine vector in cancer immunotherapy.
本研究旨在探讨聚多巴胺纳米颗粒（Pdop-NPs）作为皮下抗原递送载体在抗肿瘤治疗中的疗效。通过多巴胺在有氧和弱碱性溶液中自聚合制备纳米颗粒，并将肿瘤模型抗原卵清蛋白（OVA）接枝到纳米颗粒上，形成OVA@Pdop纳米颗粒（OVA@Pdop-NPs）。OVA@Pdop-NPs的粒径为232.8 nm，zeta电位为-23.4 mV，OVA蛋白的负载量为754 μg mg。OVA@Pdop-NPs基本无细胞毒性，甚至对骨髓来源的树突状细胞（BMDCs）表现出轻微的活力影响。与游离OVA相比，OVA@Pdop-NPs表现出更高的细胞摄取率，并且在体内更容易迁移至淋巴结。体外和体内实验均表明，OVA@Pdop-NPs可促进DCs成熟，上调主要组织相容性复合体（MHC）、共刺激分子和细胞因子的表达。当用于治疗携带OVA-MC38结肠肿瘤的小鼠时，OVA@Pdop-NPs可有效激活OVA特异性细胞毒性CD8 T细胞，并诱导记忆性CD4和CD8 T细胞的产生，从而显著抑制肿瘤生长。所有初步数据均证明了OVA@Pdop-NPs作为癌症免疫治疗疫苗载体的应用潜力。
