Abstract
Background: Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, poly lactic-co-glycolic acid (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. This study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. Methods: We developed epidermal growth factor (EGF) functionalized poly PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC NPs) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated by morphology, size distribution, in vitro stability and release profile. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Results: We found that EGF-PLGA@5Fu/PFC NPs had an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 colon cancer cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC relieved tumor hypoxia via transporting oxygen to the tumor. Conclusions: We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles might provide new potential for selective delivery of chemotherapy drugs to cancers.
Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon
