Abstract
BackgroundTumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer.MethodsWe developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of EGF-PLGA@5Fu/PFC NPs in vivo.ResultsThe findings showed that EGF-PLGA@5Fu /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, EGF-PLGA@5Fu/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, EGF-PLGA@5Fu/PFC NPs suppressed tumor growth more effectively than 5Fu, PLGA@5Fu or PLGA@5Fu/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors.ConclusionWe constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.
Highlights
Tumor recurrence and metastasis occur at a high rate in patients with colon cancer
Characterization of nanoparticles To prepare epidermal growth factor (EGF)-PLGA@5Fu/PFC NPs, 5Fu was encapsulated in PLGA polymer using the double emulsification solvent evaporation method
Dynamic light scatter analysis confirmed that the average diameter of EGF-PLGA@5Fu/PFC NPs was 200 ± 10.84 nm, with a narrow distribution (Fig. 1b)
Summary
Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. Colon cancer is one of the most common malignant cancers, and is associated with high morbidity and mortality worldwide [1]. Clinical therapeutic strategies for colon cancer include radiotherapy, chemotherapy and surgery. The efficacy of these therapeutic approaches is limited. Surgical intervention is associated with high rates of recurrence and metastasis [2]. Chemotherapeutic approaches often suffer from poor bioavailability, multidrug resistance and high system toxicity, which results in significant adverse effects and poor efficacy [3]. Development of effective strategies for the treatment of colon cancer is critical
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