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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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

• Authors: Pingping Wu, Qing Zhou, Huayun Zhu, Yan Zhuang, Jun Bao
• Journal: BMC cancer (BMC Cancer) Vol. 20 Issue 1 Pg. 354 (Apr 28 2020) ISSN: 1471-2407 [Electronic] England
• PMID: 32345258 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Carriers
• Fluorocarbons
• Polylactic Acid-Polyglycolic Acid Copolymer
• Epidermal Growth Factor
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis
• Cell Proliferation
• Colonic Neoplasms (drug therapy, pathology)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Liberation
• Drug Therapy, Combination
• Epidermal Growth Factor (chemistry)
• Female
• Fluorocarbons (chemistry, pharmacology)
• Fluorouracil (chemistry, pharmacology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (administration & dosage, chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays