Franco Centurion, Kang Lin, Shu Geng, Siti Nur Asyura Adzlan, Qingqing Fan, Federico Mazur, Ravindra Kokate, Priyank Kumar, Christina Cortez-Jugo, Frank Caruso, Rona Chandrawati
Artificial nanozymes, defined as nanomaterials that mimic enzyme-like catalytic activity, emerge as adaptable tools for biomedical applications by uniting catalytic activity with structural stability and chemical versatility. Here, we introduce liquid gallium (Ga) as a catalytic center for nitric oxide (NO) generation and demonstrate its translation into a multifunctional coating. Ga nanoparticles were stabilized with tannic acid (TA) and embedded into a TA-zirconium (TA-Zr4+) metal-phenolic network (MPN), producing robust, substrate-independent films. Ga catalyzed the decomposition of S-nitrosothiols (RSNOs) through electron transfer, enabling NO generation from both model donors such as S-nitrosoglutathione (GSNO) and endogenous precursors in human umbilical vein endothelial cells (HUVECs), with activity retained over multiple cycles. The TA-Zr4+ framework stabilized the coatings and contributed intrinsic antioxidant and anti-inflammatory activities, resulting in a platform that amplified therapeutic outcomes. Functionally, the coatings displayed tunable NO generation, enhanced intracellular NO levels in HUVECs by ∼48%, reduced pro-inflammatory cytokines TNF-α and IL-6 by ∼35% and ∼40%, respectively, under LPS stimulation, and supported endothelial biocompatibility. Together, these findings establish liquid Ga as an efficient catalyst for NO generation and present a design strategy that advances implant coatings from conventional NO donor-based systems toward active, regenerative, and multifunctional therapeutic interfaces.