Ru/Pt@BSA nanoparticles for efficient photo-catalytic oxidation of NAD(P)H and targeted cancer treatment under hypoxic conditions

Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide (2′-phosphate) (NAD(P)H) has attracted much attention for cancer therapy. However, the general oxygen-dependent mechanism heavily depresses the efficacy in hypoxic tumors. To solve this problem, herein platinum nanoparticles (Pt NPs) with catalase-like (CAT-like) and catalytic H2 evolution activities were introduced as a powerful assistant to enhance the photo-catalytic NAD(P)H oxidation of Ru1 ([Ru(phen)2(PIP-OCH3)]2+, phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4‑methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) under hypoxic and even oxygen-free conditions. Firstly, Pt NPs can transform the original and in situ formed H2O2 once again into O2 by the CAT-like activity, thus relieving tumor hypoxia and realizing cyclic utilization (at least in part) of the precious oxygen in hypoxia. Secondly, Pt NPs can also be served as H2 evolution catalysts while using Ru1 as the photosensitizer and NAD(P)H as the electron and proton donor. In this process, NAD(P)H is oxidized without the participation of oxygen, which can provide an effective way even under oxygen-free conditions. Via co-encapsulation of Ru1 and Pt NPs in bovine serum albumin (BSA) with tumor targeting ability, the resultant Ru/Pt@BSA could photo-catalyze intracellular NAD(P)H oxidation under hypoxic conditions (3% O2), and exhibited an efficient and selective anticancer activity both in vitro and in vivo. Our results may provide new sights for efficient and targeted cancer treatment under hypoxic conditions.