Anti-Colon Cancer Effect of Folic Acid-Modified Chitosan-Loaded 5-Fluorouracil Nanoparticles

Abstract

In this study, we designed a dual-targeting drug formulation that passively targets tumor tissue through the EPR effect and actively targets tumor cells through folic acid binding to folic acid receptor. 5-fluorouracil-loaded folic acid-modified chitosan nanoparticles were prepared by self-assembly, and their average sizes were determined to be 204.7±3.23 nm by dynamic light scattering measurement, and their drug loading and encapsulation rates were calculated to be 15.90% and 47.27%, respectively. MTT assay, flow cytometry and cell migration assays showed that they were more able to inhibit cell viability and cell migration of RKO cells and induce apoptosis than free 5-fluorouracil and 5-fluorouracil-loaded chitosan nanoparticles. The highest uptake efficiency of 5-fluorouracil-loaded folic acid-modified chitosan nanoparticles was observed in RKO cells in the uptake assay. In animal experiments, folic acid-modified nanoparticles inhibited tumor growth more than those of free 5FU and 5-fluorouracil-loaded chitosan nanoparticles, and histological staining results confirmed that they had the highest inhibitory effect on tumor growth. In vivo fluorescence imaging results showed that 5-fluorouracil-loaded chitosan nanoparticles and 5-fluorouracil-loaded folic acid-modified chitosan nanoparticles had good tumor targeting in nude mice, and 5-fluorouracil-loaded folic acid-modified chitosan nanoparticles had stronger targeting.