Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Abstract

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1 O 2 . We have obtained derivatives of formulas [Cp*Ir(C ∧ N)Cl] and [Cp*Ir-(C ∧ N)L]BF 4 with different degrees of π-expansion in the C ∧ N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Timedependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of halfsandwich iridium cyclometalated complexes active in PDT.

Two-Photon Photodegradation of E3 Ubiquitin Ligase Cereblon by a Ru(II) Complex: Inducing Ferroptosis in Cisplatin-Resistant Tumor Cells

“…Singlet oxygen is considered the main cytotoxic species in PDT processes . The ability of Ru-Poma to produce singlet oxygen was demonstrated by electron spin resonance (ESR) spectra in the presence of capture agent 2,2,6,6-tetramethyl-4-piperidone hydrochloride (TEMP).…”

Iridium(iii) complexes conjugated with naproxen exhibit potent anti-tumor activities by inducing mitochondrial damage, modulating inflammation, and enhancing immunity

“…3–10 Secondly, due to the strong spin–orbit coupling effect and rich photophysical and chemical properties of cyclometalated iridium( iii ) complexes, they exhibit photodynamic and photothermal activity. 11–17 In addition, iridium complexes can induce multiple modes of cell death, including apoptosis, 18,19 autophagy, 20 oncosis, 21 ferroptosis, 22 pyroptosis, 23 etc .…”

Alkaline Phosphatase Activated Near-Infrared Frequency Upconversion Photosensitizers for Tumor Photodynamic Therapy

“…Photodynamic therapy (PDT) is a treatment modality developed in the 1980s and has been used for clinical treatment in many countries with promising results. − There are advantages of noninvasiveness, no drug resistance, and low side effects, which can effectively overcome the shortcomings of traditional treatment. − The mechanism of PDT is that the photosensitizer generates singlet oxygen ( 1 O 2 ) under the excitation of light, and 1 O 2 causes certain damage to the subcellular organelles, proteins, and nucleic acids in the tumor tissue, resulting in the death of tumor cells. − Although PDT has made some achievements in tumor treatment, in vivo, the tumors cannot be effectively killed due to inadequate excitation light penetration and weak photon capture ability of photosensitizers. , However, near-infrared light is an effective PDT excitation with high tissue penetration depth, but most photosensitizers have complex synthesis and poor photostability. , It is interesting to note that frequency upconversion luminescence (FUCL) is a single photon process that relies on hot-band absorption, which offers several advantages compared to other upconversion mechanisms. For instance, it requires lower pumping power, is easily modifiable, is more readily accessible, and recently has become the focus of deep-seated cancer PDT. − The hot band absorption-associated anti-Stoke involved St, which is a real intermediate state; most of them only ameliorated the excited-state intersystem crossing (ISC) by enhancing spin–orbit coupling (SOC) via the heavy atom effect .…”