Multifunctional Modified Tumor Cell Membranes-Coated Adjuvant PTX against Melanoma

Abstract

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.

Keywords

• cell membrane
• PTX
• fusion peptide