Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

Abstract

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1–1 μM) by comparatively low dose of 405 nm light (3.6 J cm−2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

“…Platinum NPs are included in cosmetics, supplements, food additives, electrocatalytic processes, data storage systems, electronic devices, electrochemical biosensors, and chemical, fluorescence, and refractometry sensors [5][6][7]. Furthermore, PtNPs have biomedical applications as diagnostic mediators, medical implants, drug delivery vehicles, and photothermal therapy as they are less cytotoxic than other metal nanoparticles such as silver [8][9][10][11]. The biological responses of PtNPs depend on their physicochemical properties, including size, shape, surface moiety, core composition, and morphology [12].…”

Chitosan promotes ROS-mediated apoptosis and S phase cell cycle arrest in triple-negative breast cancer cells: evidence for intercalative interaction with genomic DNA

“…Recent advancements in breast cancer treatment using chemotherapy, radiotherapy, and surgery have extended the life expectancy of patients considerably. [1][2][3] However, serious side effects, low specicity and drug resistance of anticancer drugs have inspired scientists to search for more effective and harmless medication. 4 The tightly regulated apoptosis extrinsic pathway that is triggered via death receptors present on the surface of the cell, and the mitochondrial-dependent intrinsic pathway are the key factors in maintaining cellular homeostasis.…”

New cyclometalated Ir(iii) complexes with NCN pincer and meso-phenylcyanamide BODIPY ligands as efficient photodynamic therapy agents

“…[6][7][8] Some cyclometalated Ru(II), Ir(III), and Pt(II) complexes, Ru(II) arene complexes, and Re(I) tricarbonyl complexes have proven themselves for photocytotoxicity studies. [9][10][11][12][13][14][15] Cyclometalated Ir III complexes have recently received great interest for PDT agents due to their exceptional properties such as simple color tuning, energy-level control, high quantum yields, large Stokes shis, long-lived phosphorescence, and ROS generation under hypoxia conditions via electron (type I) or energy transfer (type II). [16][17][18][19][20][21][22][23][24][25][26][27] BODIPY (boron dipyrromethene) derivatives have found to be applicable as potential applications for biological labeling, cellular imaging, and uorescence sensing, unique narrow emission with high quantum yield in biological and medical elds.…”