Dinuclear Ru(II) complexes-based AIE agents with efficient type I/II ROS generation and photo-catalytic NADH oxidation trigger ferroptosis and immunogenic cell death for cancer therapy.

Abstract

Photodynamic therapy (PDT) has garnered considerable attention due to its remarkable spatiotemporal selectivity, minimal invasiveness, and low potential for drug resistance. However, traditional photosensitizers (PSs) applied in PDT usually suffer from aggregation-caused quenching (ACQ) effect, the difficulty in overcoming tumor hypoxic resistance, single and inefficient photochemical mechanism of action (MoA), poor cancer targeting ability, etc. In this work, three novel dinuclear Ru(II) complexes (Ru1-Ru3) with aggregation-induced emission (AIE) activity were developed and their structure-property relationships were systematically investigated. Among them, Ru1 can efficiently generate both type I and type II reactive oxygen species (ROS). Notably, Ru1 is also able to potently photo-oxidize reduced nicotinamide adenine dinucleotide (NADH) with a record-breaking turnover frequency (TOF) value of approximately 2688 h-1. By further loading of Ru1 in bovine serum albumin (BSA) with tumor targeting ability, the resultant Ru1@BSA could selectively accumulate in tumor tissues and efficiently inhibit tumor growth by photo-inducing ferroptosis and immunogenic cell death (ICD) on a 4T1 tumor-bearing mouse model. This work highlights dinuclear Ru(II) AIE photosensitizers as a promising platform for multimodal photodynamic cancer therapy.