Abstract
Curcumin shows a potential anticancer activity, as it is involved in signaling pathway suppressing β-catenin response transcription. In this study, the effects of curcumin released from the biocompatible and biodegradable polyaspartamide based micelles on colon cancer treatment via the Wnt/β-catenin signaling pathway are investigated. Hydrophobic octadecylamine (C18) and hydrophilic O-(2-aminoethyl) polyethylene glycol (PEG) were grafted on a polysuccinimide (PSI) backbone for micelle formation. Folic acid (FA) was employed to facilitate the targeting activity to colon cancer cells and curcumin was conjugated via acid cleavable linkage, hydrazone (Hyd) to provide the pH sensitive drug release. Two types of micellar structures, Folate-PEG/Hyd-Curcumin/C18-g-PSI (FA-Cur) and PEG/Hyd-Curcumin/C18-g-PSI (NFA-Cur), were synthesized and their chemical structure was identified by 1H NMR spectroscopy. The cytotoxicity carried out by MTT assay informed that the cell viability of FA-Cur treated SW480 was much lower than that of NFA-Cur treated one at the concentration > 0.25 μg mL−1. Western blot assay showed that FA-Cur inhibited the target genes, cyclin D1 and c-myc, more strongly than NFA-Cur at the concentration > 0.5 μg mL−1. From these results, FA-Cur micelles are expected to be a promising candidate for colon anti-cancer via inhibiting Wnt/β-catenin pathway.
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