EpCAM aptamer activated 5-FU-loaded PLGA nanoparticles in CRC treatment; in vitro and in vivo study.

In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide--glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). experiments revealed that Ap-FU-NPs had a superior cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells.