Multifunctional TK-VLPs nanocarrier for tumor-targeted delivery

Abstract Virus-like particles (VLPs) have been exploited for various biomedical applications, such as the monitoring, prevention, diagnosis and therapy of disease. In this study, a novel multifunctional VLPs nanocarrier (TK-VLPs) was prepared and used for tumor-targeted delivery. The SPR and cell uptake results indicated that the TK peptide is a “bi-functional ligand” with high affinity for Caco-2, HRT-18 and HUVEC cells through the integrin α 6β1 and integrin α vβ3 receptors. The results of the direct immunofluorescence, SDS-PAGE and western blot assays demonstrated that the TK-VLPs were successfully prepared using the baculovirus expression system. Confocal laser scanning microscopy and the flow cytometry analysis validated that the TK-VLPs could target to Caco-2, HRT-18 and HUVEC cells. An in vivo study further confirmed that the TK-VLPs could target and efficiently deliver fluorescein to tumor cells and the tumor vasculature in mice bearing subcutaneous tumors. TK-VLPs-DOX displayed a uniform, spherical shape and an average size of approximately 28 nm. The results of the cell uptake and cytotoxicity assays indicated that TK-VLPs-DOX could enhance the selectivity for colorectal cancer cells. Together, our studies provide strong evidence that TK-VLPs could target colon tumor cells and tumor angiogenesis with enhanced permeability and retention effects , suggesting that the TK-VLPs are a multifunctional nanocarrier with potential applications in a colon tumor-targeted drug delivery system.