Folic acid-conjugated magnetic triblock copolymer nanoparticles for dual targeted delivery of 5-fluorouracil to colon cancer cells

Background: In the current study, folic acid-conjugated PEG-PCL-PEG triblock copolymer were synthesized and loaded with 5-fluorouracil and magnetite nanoparticles (5-FU-SPION-PEG-PCL-PEG-FA) for targeted delivery of drug to HT29 human colon cancer cells and CT26 mouse colon cancer model. The nanoparticles were synthesized and characterized by nuclear magnetic resonance spectroscopy (NMR) and transmission electron microscopy (TEM). The cellular uptake of nanoparticles was assessed in vitro (on HUVEC and HT29) and in vivo (on CT26 colon tumor tissues). The cytotoxic effect of nanoparticles was assessed on human colon cell lines (HT29, Caco-2, HTC116, and SW480) and normal HUVEC cells. In addition, antitumor effects of nanoparticles were investigated based on tumor volume, survival time and protein expression of Bax and Bcl-2 on CT26 tumor-bearing BALB/c mice. Results: Characterization of nanoparticles showed 5-FU-SPION-PEG-PCL-PEG-FA (5-FU-NPs-FA) nanoparticles had spherical shape with hydrodynamic diameter of 85 nm. The drug-release profile exhibited sustained pH-responsive release with cumulative release reaching approximately 23% after 24 h. Cellular uptake studies revealed that HT29 cancer cells absorb higher amount of 5-FU-NPs-FA as compared to HUVEC normal cells (P < 0.05). In addition, 5-FU-NPs-FA was found to be more antitumor efficient in comparison to free 5-FU based on Bax/Bcl2 ratio, survival rate of tumoral mouse and inhibitory tumor volume (P < 0.05). Conclusions: The results suggested that 5-FU-NPs-FA could be considered as promising sustained drug delivery platform for in vitro and in vivo conditions, which may provide selective treatment of tumor cancer cells. [GRAPHICS] .

Automated summary

In this study, folic acid-conjugated PEG-PCL-PEG triblock copolymer loaded with 5-fluorouracil and magnetite nanoparticles was synthesized for targeted delivery of drugs to colon cancer cells. The nanoparticles exhibited sustained drug release and showed effective cellular uptake and antitumor activity in both in vitro and in vivo experiments.