Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(II)-cyanine complex has been designed to...

Due to conventional photodynamic therapy encountering serious problems of phototoxicity and low tissue-penetrating depth of light, other dynamic therapy-based therapeutic methods such as sonodynamic therapy (SDT) are expected to be developed. To improve the therapeutic response to SDT, more effective sonosensitizers are imperative. In this study, a novel water-soluble iridium­(III)-porphyrin sonosensitizer (IrTMPPS) was synthesized and used for SDT. IrTMPPS generated ample singlet oxygen (1O2) under US irradiation and especially showed distinguished US-activatable abilities at more than 10 cm deep-tissue depths. Interestingly, under US irradiation, IrTMPPS sonocatalytically oxidized intracellular NADH, which would enhance SDT efficiency by breaking the redox balance in the tumor. Moreover, IrTMPPS displayed great sonocytotoxicity toward various cancer cells, and in vivo experiments demonstrated efficient tumor inhibition and anti-metastasis to the lungs in the presence of IrTMPPS and US irradiation. This report gives a novel idea of metal-based sonosensitizers for sonotherapy by fully taking advantage of non-invasiveness, water solubility, and deep tumor therapy.

The curative effect of sorafenib in hepatocellular carcinoma (HCC) is limited and sorafenib resistance remains a major obstacle for HCC. To overcome this obstacle, a new photoactive sorafenib-Ru­(II) complex Ru-Sora has been designed. Upon irradiation (λ = 465 nm), Ru-Sora rapidly releases sorafenib and generates reactive oxygen species, which can oxidize intracellular substances such as GSH. Cellular experiments show that irradiated Ru-Sora is highly cytotoxic toward Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared to sorafenib, Ru-Sora has a significant photoactivated chemotherapeutic effect against Hep-G2-SR cancer cells and 3D Hep-G2 multicellular tumor spheroids. Furthermore, Ru-Sora inducing apoptosis and ferroptosis is proved by GSH depletion, GPX4 downregulation, and lipid peroxide accumulation. Metabolomics results suggest that Ru-Sora exerts photocytotoxicity by disrupting the purine metabolism, which is expected to inhibit tumor development. This study provides a promising strategy for enhancing chemotherapy and combating drug-resistant HCC disease.

Rationally-designed glucose-appended Ir(III) photo-catalysts ([Ir(N,C)2(N,N-Glc)]+, Ir1-Ir3) show visible light-induced catalytic NAD(P)H oxidation in aqueous solution. Highly in-vivo biocompatible complex, Ir3, shows lysosome and mitochondria targeting necro-apoptotic photo-cytotoxicity against various cancer...

Photoactive antibacterial therapy is one of the novel therapeutic methods that has great application potential and prospects for curbing bacterial infections. In this work, a photoactivated iridium complex (Ir–Cl) is synthesized for photoactive antibacterial research. Ir–Cl exhibits photoacidolysis, which can generate H+ and be converted into a photolysis product Ir–OH under blue light irradiation. At the meantime, this process is accompanied by 1O2 generation. Notably, Ir–Cl can selectively permeate S. aureus and exhibit excellent photoactive antibacterial activity. Mechanism studies show that Ir–Cl can ablate bacterial membranes and biofilms under light irradiation. Metabolomics analysis proves that Ir–Cl with light exposure mainly disturbs some amino acids’ degradation (e.g., valine, leucine, isoleucine, arginine) and pyrimidine metabolism, which indirectly causes the ablation of biofilms and ultimately produces irreversible damage to S. aureus. This work provides guidance for metal complexes in antibacterial application.