School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC.
Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC; Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
J Control Release. 2022 Nov;351:970-988. doi: 10.1016/j.jconrel.2022.10.002. Epub 2022 Oct 12.
Cancer vaccines have recently garnered tremendous interest. However, the targeted delivery of antigens and adjuvants to dendritic cells (DCs) still remains challenging. In this study, we developed glycosylated poly(lactic-co-glycolic acid) nanoparticles (NPs) loaded with the SIINFEKL peptide (OVA) as a tumor-specific antigen and CpG oligodeoxynucleotide (CpG) as an adjuvant for an effective DC-targeted cancer vaccine. Surface modification of NPs with galactose (Gal) or mannose (Man) was carried out by a double-emulsion solvent evaporation method, and the products were respectively named OVA-CpG Gal-NPs and OVA-CpG Man-NPs. They exhibited a uniform particle size, high loading capacity, robust stability, and extended release. The OVA-CpG Gal-NPs were found to rapidly enhance antigen uptake and DC maturation. In the in vivo study, OVA-CpG Gal-NPs via intravenous (i.v.), intranasal (i.n.) and subcutaneous (s.c.) routes had rapidly accumulated in the spleen. Moreover, the non-glycosylated OVA-CpG NPs after s.c. immunization could rapidly be trafficked to distal lymph nodes and sustained higher levels. All of these formulations increased the level of cluster of differentiation 4-positive (CD4) T cells and interferon (IFN)-γ in the spleen, then promoted the cytotoxic CD8 tumor-infiltrating lymphocytes against E.G7-OVA lymphomas. In conclusion, galactosylated NPs provided an effective platform to enhance the DC targeting to induce cellular immunity and T-cell recruitment into tumor sites in vivo, thus showing great potential to be developed as a prophylactic vaccine for cancer immunotherapy.
癌症疫苗最近引起了极大的关注。然而，将抗原和佐剂靶向递送至树突状细胞（DC）仍然具有挑战性。在这项研究中，我们开发了负载 SIINFEKL 肽（OVA）作为肿瘤特异性抗原和 CpG 寡脱氧核苷酸（CpG）作为佐剂的糖基化聚（乳酸-共-乙醇酸）纳米颗粒（NPs），用于有效的 DC 靶向癌症疫苗。通过双重乳液溶剂蒸发法对 NPs 进行半乳糖（Gal）或甘露糖（Man）表面修饰，分别命名为 OVA-CpG Gal-NPs 和 OVA-CpG Man-NPs。它们表现出均匀的粒径、高载药量、强大的稳定性和延长的释放。研究发现，OVA-CpG Gal-NPs 可快速增强抗原摄取和 DC 成熟。在体内研究中，OVA-CpG Gal-NPs 通过静脉（i.v.）、鼻内（i.n.）和皮下（s.c.）途径快速积聚在脾脏中。此外，皮下免疫后未糖基化的 OVA-CpG NPs 可快速转运至远端淋巴结并维持更高水平。所有这些制剂均增加了脾脏中 CD4 阳性（CD4）T 细胞和干扰素（IFN）-γ的水平，然后促进了针对 E.G7-OVA 淋巴瘤的细胞毒性 CD8 肿瘤浸润淋巴细胞。总之，半乳糖化 NPs 提供了一个有效的平台，可增强 DC 靶向作用，在体内诱导细胞免疫和 T 细胞募集到肿瘤部位，因此具有作为癌症免疫治疗预防性疫苗的巨大潜力。
