An in-vitro study of active targeting & anti-cancer effect of folic acid conjugated chitosan encapsulated indole curcumin analogue nanoparticles.

Natural compounds like Curcumin with anti-cancer, anti-inflammatory and anti-bacterial properties are good target for drug development but its poor aqueous solubility, bioavailability, and low retention properties makes it a poor drug candidate in clinical settings. Here in this study, we have used an indole curcumin analogue (ICA) that has better bioavailability and enhanced permeability and retention (EPR) effect than curcumin. To make an active targeting drug we have designed folic acid conjugated chitosan-based nanoparticles encapsulating Indole curcumin analogue (CS-FA-ICA-np). The physical characteristics of CS-FA-ICA-np were evaluated by DLS, SEM, FTIR, XPS, XRD and TGA. Anti-cancer activity was analyzed using MTT, Fluorescence staining, Flow cytometry, comet assay, DNA fragmentation assay, wound healing, gelatin zymography, chick chorioallantoic membrane (CAM) assay and hemolysis assay. The size of CS-FA-ICA-nps were found to be 111 nm, and spherical in shape as observed in SEM. In-vitro assays show that CS-FA-ICA np has IC₅₀ of 90 μg/mL in MDA-MB-231, increases ROS concentration, arrests cell cycle in G2-M phase, reduces matrix metalloproteinase-9 (MMP-9) activity and initiates apoptosis in cancer cells. Our results indicate that encapsulation of ICA increases its anti-cancer effect, drug stability, enhanced drug delivery to cancer microenvironment.