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 photo-activated 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-1)(L-2)] (1), where L-1 is bis(3,5 di-tert-butyl-2-hydroxybenzyl)glycine and L-2 is 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthroline-5-yl)pentanamide, and the gold nanocomposite functionalized with complex 1 (1-AuNPs) are reported. There was a significant red shift in the UV-visible absorption band on functionalization of complex 1 to the gold nanoparticles (lambda(max): 573 nm, 1; lambda(max): 660 nm, 1-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 (1-AuNPs) to A549 (IC50: 0.006 mu M) and HaCaT (IC50: 0.0075 mu M) cells in red light (600-720 nm, 30 J/cm(2)) while almost nontoxic (IC50 > 500 mu g/mL, 0.053 mu M) in the dark, (ii) the nontoxicity of 1-AuNPs to normal human diploid fibroblasts (WI-38) or human peripheral lung epithelial (HPL1D) cells (IC50 > 500 mu g/mL, 0.053 mu M) both in the dark and red light signifying the target-specific anticancer activity of the nanocomposite, (iii) localization of 1-AuNPs in mitochondria and partly nucleus, (iv) remarkable red light-induced generation of reactive oxygen species (ROS: O-1(2), (OH)-O-center dot) 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 1 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 (1-AuNPs) as the emerging next-generation iron-based photochemotherapeutic agent for targeted cancer treatment modality.

Automated summary

Iron(III)-phenolate/carboxylate complexes have potential for photo-activated chemotherapy. A new red light-absorbing iron(III)-phenolate/carboxylate complex-functionalized gold nanocomposite showed remarkable photocytotoxicity in adenocarcinomic human immortalized keratinocytes and alveolar basal epithelial cells.