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

Pal, M and Upadhyay, A and Masarkar, N and Bera, A and Mukherjee, S and Roy, M (2023) 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. In: Dalton Transactions, 53 (5). pp. 2108-2119.

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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. © 2024 The Royal Society of Chemistry.

Item Type:	Journal Article
Publication:	Dalton Transactions
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs toRoyal Society of Chemistry.
Keywords:	Cancer cells; Cell death; Chemical activation; Diseases; Electron spin resonance spectroscopy; Gold; Iron compounds; Lanthanum compounds, Cancer cells; Cellular uptake; Folates; Functionalized; Light activation; MDA-MB-231; Photocytotoxicity; Red light; Triple negative; UV-visible, Charge transfer, folic acid; gold; iron; metal nanoparticle; nanoconjugate, chemistry; HeLa cell line; human; MDA-MB-231 cell line; neoplasm, Folic Acid; Gold; HeLa Cells; Humans; Iron; MDA-MB-231 Cells; Metal Nanoparticles; Nanoconjugates; Neoplasms
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	04 Mar 2024 09:01
Last Modified:	04 Mar 2024 09:01
URI:	https://eprints.iisc.ac.in/id/eprint/84213

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