DOI: 10.1002/advs.77143 ISSN: 2198-3844

Liquid Gallium Nanozyme Coatings Enable Sustained Nitric Oxide Generation With Antioxidant and Anti‐Inflammatory Functions

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

ABSTRACT

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‐Zr 4+ ) 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‐Zr 4+ 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.

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