Folate-assisted targeted photocytotoxicity of red-light-activable iron(iii) complex co-functionalized gold nanoconjugates (Fe@FA-AuNPs) against HeLa and triple-negative MDA-MB-231 cancer cells

Abstract

Photo-redox chemistry resulting from ligand to metal charge transfer in red-light-activable iron(III) complexes could be a potent strategic tool for next-generation photochemotherapeutic applications. Herein, we developed an iron(III) complex and folate co-functionalized gold nanoconjugate (Fe@FA-AuNPs) and thoroughly characterized it with NMR, ESI MS, UV–visible, EPR, EDX, XPS, powder X-ray diffraction, TEM and DLS studies. There was a remarkable shift in the SPR band of AuNPs to 680 nm, and singlet oxygen (¹O₂) and hydroxyl radicals were potently generated upon red-light activation, which were probed by UV–visible and EPR spectroscopic assays. Cellular uptake studies of the nanoconjugate (Fe@FA-AuNPs) revealed significantly higher uptake in folate(+) cancer cells (HeLa and MDA-MB-231) than folate(−) (A549) cancer cells or normal cells (HPL1D), indicating the targeting potential of the nanoconjugate. Confocal imaging indicated primarily mitochondrial localization. The IC₅₀ values of the nanoconjugate determined from a cell viability assay in HeLa, MDA-MB-231, and A549 cells were 27.83, 39.91, and 69.54 μg mL⁻¹, respectively in red light, while in the dark the values were >200 μg mL⁻¹; the photocytotoxicity was correlated with the cellular uptake of the nanoconjugate. The nanocomposite exhibited similar photocytotoxicity (IC₅₀ in red light, 37.35 ± 8.29 μg mL⁻¹ and IC₅₀ in the dark, >200 μg mL⁻¹). Mechanistic studies revealed that intracellular generation of ROS upon red-light activation led to apoptosis in HeLa cells. Scratch-wound-healing assays indicated the inhibition of the migration of MDA-MB-231 cells treated with the nanoconjugate and upon photo-activation. Overall, the nanoconjugate has emerged as a potent tool for next-generation photo-chemotherapeutics in the clinical arena of targeted cancer therapy.