Folic Acid Receptor-Mediated Targeting Enhances the Cytotoxicity, Efficacy, and Selectivity of Withania somnifera Leaf Extract: In vitro and in vivo Evidence

Nanomedicine holds great potential for drug delivery to achieve more effective and safer cancer treatment. Earlier, we reported that the alcoholic extract of leaves (i-Extract) has selective cancer cell killing activity. Herein, we developed a folate receptor-targeting i-Extract nanocomplex (FRi-ExNC) that suspends well in water and possesses enhanced selective anticancer activity in both and assays. Comparative analyses of folate receptor (FR)-positive and -negative cells revealed that FRi-ExNC caused a stronger decrease in Cyclin D/Cdk4 and anti-apoptotic protein Bcl-2, as well as a higher increase in the growth arrest regulating protein p21 and pro-apoptotic protein PARP-1, in FR-enriched cancer cells. Our results demonstrate that FRi-ExNC could be a natural source-based nanomedicine for targeted cancer therapy.