Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China.
Int J Pharm. 2019 Apr 5;560:1-10. doi: 10.1016/j.ijpharm.2019.01.027. Epub 2019 Jan 21.
Cancer immunotherapy is considered to be one of the alternatives to traditional chemotherapy. It's known that foreign antigen, such as ovalbumin (OVA), can label tumor cells, leading to neoantigen recognition by cytotoxic T lymphocytes. Herein, a novel multifunctional micelle coated with PEGylated hyaluronic acid (HA) was prepared through self-assembly and electrostatic interaction. The OVA-loaded micelle with uniform size (132.1 ± 0.2 nm in diameter) exhibited favorable stability and sustained release profiles. The HA-coated micelle could target CD44-overexpressed cells and enhance the cellular uptake of OVA by 11.9 fold compared to free OVA. In vitro studies revealed that the cationic polymer, polyethyleneimine, could facilitate endosomal escape of OVA to label a tumor cell. After treatment with the OVA-loaded micelle, tumor growth in mice was significantly inhibited by 70% compared to the group treated with free OVA. All these results suggest the potential application of the immunotherapeutic micellar platform for melanoma treatment.
癌症免疫疗法被认为是传统化疗的替代方法之一。已知外源性抗原，如卵清蛋白 (OVA)，可以标记肿瘤细胞，导致细胞毒性 T 淋巴细胞识别新抗原。本文通过自组装和静电相互作用制备了一种包覆有聚乙二醇化透明质酸 (HA) 的新型多功能胶束。载 OVA 的胶束具有均匀的粒径（直径为 132.1±0.2nm），表现出良好的稳定性和持续释放特性。HA 包覆的胶束可以靶向 CD44 过表达的细胞，并将 OVA 的细胞摄取量提高 11.9 倍，而游离 OVA 仅提高 11.9 倍。体外研究表明，阳离子聚合物聚乙烯亚胺可以促进 OVA 的内体逃逸，从而标记肿瘤细胞。与游离 OVA 处理组相比，用载 OVA 的胶束处理后，小鼠肿瘤生长显著抑制了 70%。所有这些结果表明，免疫治疗性胶束平台具有用于治疗黑色素瘤的潜力。
