La(iii)-curcumin-functionalized gold nanocomposite as a red light-activatable mitochondria-targeting PDT agent

Musib, D and Ramu, V and Raza, MK and Upadhyay, A and Pal, M and Kunwar, A and Roy, M (2022) La(iii)-curcumin-functionalized gold nanocomposite as a red light-activatable mitochondria-targeting PDT agent. In: Inorganic Chemistry Frontiers, 9 (4). pp. 686-701.

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Abstract

Red light-activatable transition metal complexes have recently emerged as viable materials for use in photodynamic/photochemotherapeutic applications. Ideal photosensitizers or photochemotherapeutic agents are still an elusive goal. Herein, we report the synthesis, characterization and remarkable photodynamic activity of the [LaIII(Cur)2(L1)(NO3)] (1)-functionalized gold nanocomposite, 1-AuNPs, where Cur represents curcumin and L1 represents 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthroline-5-yl)pentanamide. Functionalization of complex 1 to gold nanoparticles led to a remarkable red shift (λmax, 755 nm) in the surface plasmon resonance (SPR) band, making the La(iii)-curcumin-functionalized nanocomposite (1-AuNPs) an ideal photo-sensitizer for use in photodynamic applications. Several photophysical assays confirmed its high efficacy in generating singlet oxygen [ϕ(1O2), 0.69] through a type-II photo-process. TD-DFT calculations also predicted the presence of a low-lying triplet excited state and efficient intersystem crossing for the nanoconjugate. The log P values along with the high binding affinity of the 1-AuNPs to serum albumin predicted cellular permeability and transportation through blood. Flowcytometric analysis indicated the selective accumulation and retention of 1-AuNPs in adenocarcinomic human alveolar basal epithelial cells (A549) compared with normal alveolar fibroblast cells (WI-38). Confocal microscopy confirmed the localization of the nanocomposite in mitochondria. The nanoconjugate, 1-AuNPs, exhibited remarkable photodynamic activity against adenocarcinomic human alveolar basal epithelial cells (A549) (IC50: 25 μg mL-1 in light; >500 μg mL-1 in dark) and immortalized human keratinocytes (HaCaT) (IC50: 34 μg mL-1 in light; >500 μg mL-1 in dark) under red light (600-720 nm, 30 J cm-2), with remarkable photo-indices (PI > 20). Red light-induced generation of 1O2 by 1-AuNPsin vitro was found to be primarily responsible for the upsetting of the mitochondrial membrane potential (MMP), which led to caspase-3 activated apoptosis in A549 cells via an intrinsic pathway. During apoptosis, the pro-apoptotic BAX protein was upregulated, while the antiapoptotic Bcl-2 protein was downregulated and responsible for apoptosis after the A549 cells were treated with the red light activated nanoconjugate (1-AuNPs). Overall, the La(iii)-curcumin-functionalized gold nanocomposite is an ideal next generation La(iii)-based photosensitizer for use in photodynamic applications.

Item Type:	Journal Article
Publication:	Inorganic Chemistry Frontiers
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to the Royal Society of Chemistry.
Keywords:	Binding energy; Cell culture; Excited states; Gold nanoparticles; Lanthanum compounds; Metal nanoparticles; Mitochondria; Nanocomposites; Probes; Surface plasmon resonance, A549 cells; Curcumin; Epithelial cells; Functionalized; Gold nanocomposites; Mitochondrias; PDT agents; Photodynamic activities; Photosensitiser; Red light, Photosensitizers
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	29 Jun 2022 06:53
Last Modified:	29 Jun 2022 06:53
URI:	https://eprints.iisc.ac.in/id/eprint/73851

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