Conventional chemotherapy using small molecule drugs is marred by several challenges such as short half-life, low therapeutic index and adverse systemic side effects. In this regard, targeted therapies using ligand directed polyamidoamine (PAMAM) dendrimers could be a promising strategy to specifically deliver anticancer drugs to cancer cells overexpressing complementary receptor binding domains. The aim of this study was to utilize folate decorated PAMAM to enhance the aqueous solubility of a highly hydrophobic but very potent anticancer flavonoid analogue, 3,4-difluorobenzylidene diferuloylmethane (CDF) and to deliver it specifically to folate receptor overexpressing cervical cancer cells (HeLa) and ovarian cancer cells (SKOV3). As compared to the non-targeted formulation, the targeted formulation exhibited significant anticancer activity with higher accumulation in folate receptor overexpressing cells, larger population of apoptotic cancer cells, elevated expression of tumor suppressor phosphatase and tensin homolog (PTEN), and inhibition of nuclear factor kappa B (NF kappa B) which further confirmed the targeting ability and the promising anticancer activity of the folate based nanoformulation. (C) 2016 Elsevier Inc. All rights reserved.