NIR-Mediated Pyroelectric Catalysis for Sustained ROS/RNS Generation and Advanced Cancer Therapy In Vivo via Injectable Hydrogel

Exogenous electrical stimulation has attracted considerable attention due to the advantages of microelectric induction and subsequent biological effects such as actin reorganization and reactive oxygen species (ROS) generation. Herein, an injectable hydrogel of BPR-ARG@Gel (BAG) with pyroelectric BPR nanoparticle loading and l-arginine (ARG) introduction was fabricated for advanced cancer therapy in vivo. Due to the photothermal effect, the holes and electrons in BPR nanoparticles were separated to produce an open-circuit voltage and consequently catalyze water H₂O to generate toxic superoxide (^•O₂^-) and hydroxyl radicals (^•OH). These ROS substances further oxidize ARG to produce NO for synergistic tumor treatments. The mice experiments indicated that the employment of BAG hydrogel incorporation with a near-infrared laser downregulated the heat shock protein and recruited immune cells with 5-fold-enhanced expression of proinflammatory cytokines of interferon-γ. It was also noteworthy that the injectable hydrogel of BAG substantially induced the generation of reactive oxygen/nitrogen species (ROS/RNS) with reliable biosafety and strong tumor inhibition. Overall, these findings have provided potentially new inspirations and a feasible strategy to translate this multifunctional hydrogel toward tumor therapy in a pyroelectric stimulation manner.