Iron(III) Complex-Functionalized Gold Nanocomposite as a Strategic Tool for Targeted Photochemotherapy in Red Light.

Iron(III)-phenolate/carboxylate complexes exhibiting photoredox chemistry and photoactivated reactive oxygen species (ROS) generation at their ligand-to-metal charge-transfer (LMCT) bands have emerged as potential strategic tools for photoactivated chemotherapy. Herein, the synthesis, in-depth characterization, photochemical assays, and remarkable red light-induced photocytotoxicities in adenocarcinomic human immortalized human keratinocytes (HaCaT) and alveolar basal epithelial (A549) cells of iron(III)-phenolate/carboxylate complex of molecular formula, [Fe(L)(L)] (), where L is bis(3,5 di--butyl-2-hydroxybenzyl)glycine and L is 5-(1,2-dithiolan-3-yl)--(1,10-phenanthroline-5-yl)pentanamide, and the gold nanocomposite functionalized with complex (-AuNPs) are reported. There was a significant red shift in the UV-visible absorption band on functionalization of complex to the gold nanoparticles (λ: 573 nm, ; λ: 660 nm, -AuNPs), rendering the nanocomposite an ideal candidate for photochemotherapeutic applications. The notable findings in our present studies are (i) the remarkable cytotoxicity of the nanocomposite (-AuNPs) to A549 (IC: 0.006 μM) and HaCaT (IC: 0.0075 μM) cells in red light (600-720 nm, 30 J/cm) while almost nontoxic (IC > 500 μg/mL, 0.053 μM) in the dark, (ii) the nontoxicity of -AuNPs to normal human diploid fibroblasts (WI-38) or human peripheral lung epithelial (HPL1D) cells (IC > 500 μg/mL, 0.053 μM) both in the dark and red light signifying the target-specific anticancer activity of the nanocomposite, (iii) localization of -AuNPs in mitochondria and partly nucleus, (iv) remarkable red light-induced generation of reactive oxygen species (ROS: O, OH) in vitro, (v) disruption of the mitochondrial membrane due to enhanced oxidative stress, and (vi) caspase 3/7-dependent apoptosis. A similar cytotoxic profile of complex was another key finding of our studies. Overall, our current investigations show a new red light-absorbing iron(III)-phenolate/carboxylate complex-functionalized gold nanocomposite (-AuNPs) as the emerging next-generation iron-based photochemotherapeutic agent for targeted cancer treatment modality.