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This microenvironment is accompanied by long\u2010term suppression of endogenous antioxidant systems, which makes their clinical management extremely challenging. To address this issue, a hybridized novel gold\u2010palladium (AuPd) nanoshell of the injectable\/injectable hydrogel system UiO\/AuPd<jats:sub>shells<\/jats:sub>\/BNN6\/PEG@Gel (UAPsBP@Gel) is developed. The system is capable of acting as a nitric oxide (NO) reactor utilizing synergistic therapy that harnesses NIR\u2010II light\u2010triggered photothermal effects and controlled release of NO gas for synergistic treatment to eradicate biofilm infections at different depths. The AuPd nanoshells exhibits superoxide dismutase (SOD)\u2010, glucose oxidase (GOx)\u2010, and catalase (CAT)\u2010like activities, enabling self\u2010cascade process for scavenging both reactive oxygen species (ROS) and glucose. 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