A targeted and efficient CDT system with photocatalytic supplement of H2O2 and hydroxyl radical production at a neutral pH

The bottleneck problems of chemodynamic therapy (CDT) are the dependence on an acidic pH (2.0–4.0), insufficient H2O2 level in tumor tissues, and potential systematic toxicity of inorganic nanomaterials-based CDT agents. In this study, the new tricks of two old compounds, i.e. [Ru(phen)2(PIP-OCH3)](PF6)2 (Ru3, phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4-methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) and Fe(tpy)Cl3 (tpy = 2,2′:6′,2′-terpyridine), were harnessed to construct an ideal CDT system. Ru3 was able to efficiently photo-catalyze NADH oxidation accompanied by the production of H2O2in situ with a high yield of 73.2%, which can be converted into cytotoxic hydroxyl radicals by the biocompatible Fe(tpy)Cl3 at a neutral pH. By loading both Ru3 and Fe(tpy)Cl3 in tumor-targeting bovine serum albumin (BSA), the obtained BSA@Fe/Ru nanoparticles exhibited a highly efficient, selective, and photo-controlled CDT activity both in vitro and in vivo. This work may provide new sights for overcoming the issues confronted in CDT.