Enhanced antitumor efficacy in colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon

• Published in: BMC cancer 2020-04, Vol.20 (1), p.354-10, Article 354
• Main Authors: Wu, Pingping, Zhou, Qing, Zhu, Huayun, Zhuang, Yan, Bao, Jun
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Analysis; Animal experimentation; Animal research; Animals; Antibodies; Antimetabolites, Antineoplastic - pharmacology; Antitumor activity; Apoptosis; Bioavailability; Cancer; Cancer therapies; Cell Proliferation; Cell viability; Chemotherapy; Cholecystokinin; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colorectal cancer; Cytotoxicity; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug Liberation; Drug therapy; Drug Therapy, Combination; Drugs; Efficiency; EGF; Epidermal growth factor; Epidermal Growth Factor - chemistry; FDA approval; Female; Flow cytometry; Fluorocarbons - chemistry; Fluorocarbons - pharmacology; Fluorouracil; Fluorouracil - chemistry; Fluorouracil - pharmacology; Glycolic acid; Health aspects; Humans; Hypoxia; Immunofluorescence; Laboratory animals; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Perfluorocarbon; Perfluorocarbons; pH effects; PLGA nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polylactide-co-glycolide; Solvents; Tumor Cells, Cultured; Tumors; Vehicles; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-06803-7

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. 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. We 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. The 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. We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.