Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315000, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Biomolecules. 2023 Jan 14;13(1):179. doi: 10.3390/biom13010179.
Melanoma is the deadliest type of skin cancer. Anti-tumor immunotherapy has made great progress in increasing the overall survival of patients. However, many physiological barriers cause low bioavailability of drugs. Cell membranes are becoming increasingly prevalent for assisting drug delivery because of the significant benefits of avoiding host cell barriers. Herein, B16F10 cell membranes (BFMs) were prepared in this study. BFMs could not only act as antigens but also serve as vesicles for vaccines. To trigger potent immunity, BFMs must be taken up by dendritic cells (DCs) and combined with adjuvants to make BFMs overcome the immune tolerance. To avoid circulating BFMs into tumors and quickly internalized by DCs after subcutaneously injection, the antigen-cell penetrating fusion peptide WT(YGRKKRRQRSRRYVDFFVWL) was used to modify BFMs. Additionally, a low dosage of paclitaxel (PTX) can activate DCs via toll-like receptor-4 (TLR-4). Therefore, we developed PTX-loaded micelles using Pluronic F127. Then, WT-modified BFMs (WT-BFMs) were coated F127-PTX to yield WT-BFMs/ F127-PTX. Optimized WT-BFMs/F127-PTX promoted the cellular uptake and showed remarkable efficacy in eliciting robust antigen-specific cellular and humoral immune responses.
黑色素瘤是最致命的皮肤癌类型。抗肿瘤免疫疗法在提高患者总体生存率方面取得了重大进展。然而，许多生理屏障导致药物的生物利用度较低。由于细胞膜可以避免宿主细胞屏障，因此越来越多地被用于辅助药物递送。本研究制备了 B16F10 细胞膜（BFMs）。BFMs 不仅可以作为抗原，还可以作为疫苗的囊泡。为了引发有效的免疫反应，BFMs 必须被树突状细胞（DCs）摄取并与佐剂结合，以使 BFMs 克服免疫耐受。为了避免循环 BFMs 进入肿瘤并在皮下注射后迅速被 DCs 内化，使用抗原-细胞穿透融合肽 WT（YGRKKRRQRSRRYVDFFVWL）修饰 BFMs。此外，低剂量的紫杉醇（PTX）可以通过 Toll 样受体 4（TLR-4）激活 DCs。因此，我们使用 Pluronic F127 开发了载紫杉醇的胶束。然后，用 WT 修饰的 BFMs（WT-BFMs）包被 F127-PTX，得到 WT-BFMs/F127-PTX。优化后的 WT-BFMs/F127-PTX 促进了细胞摄取，并在引发强烈的抗原特异性细胞和体液免疫反应方面显示出显著的疗效。
