Near-infrared band responsive ROS regulator selectively inhibits breast cancer cells by programming combination phototherapy

Abstract

Catalytic therapy can effectively kill tumor cells and inhibit tumor growth by producing highly toxic reactive oxygen species (ROS). However, the long-term catalysis of nanozymes easily lead to ROS breaking through the boundary in tumor tissues, resulting in spillover and injuring normal cells. Therefore, how to control the threshold of ROS production from nanozymes in tumor tissues is an unsolved problem. In this work, to prevent the boundary effect of the photosensitizer ([Ru(bpy)2(tip)]²⁺, RBT) during ROS generation, we used the sensitivity of RBT and PdH_0.2–Ir with different wavelengths of near-infrared light (NIR) to generate ROS and H₂, respectively. Therefore, an intelligent nanosystem PdH_0.2–Ir@RBT(PIH@R) was constructed to precisely control ROS generation by adjusting the NIR laser wavelength. The palladium–iridium alloy (Pd–Ir) nanoparticles as the core can co-load hydrogen (H₂) and RBT and show NIR-responsive behaviors. Under 808 nm laser irradiation, PIH@R produces ROS with the photocatalysis of RBT, while under 1064 nm laser irradiation PIH@R will quickly activate and release H₂ to eliminate ROS. Interestingly, in vitro and in vivo experiments showed that PIH@R acted like a “Trojan horse”: PIH@R can destroy the mitochondria of 4T1 cells to destroy their redox homeostasis system, resulting in cancer cells relying on exogenous PIH@R to change their reactive oxygen species levels. Subsequently, when PIH@R is activated into a harmful oxidation state, it can easily crush the redox homeostasis system of cancer cells and induce cancer cell apoptosis.