Synergistic photothermal and antioxidant effects of chiral gold helical nanorods @CeO2 nanomaterials for accelerated infected wound healing

ABSTRACT: Bacterial infection is a major cause that impedes wound healing. Conventional antibiotic-based treatments, while aimed at suppressing infections, often lead to the emergence of drug resistance. Furthermore, monotherapeutic strategies are frequently inadequate in managing the accompanying inflammation and oxidative stress that follow infection. This work developed chiral gold helical nanorods (AuHNRs)@CeO 2 nanomaterials with photothermal bactericidal and reactive oxygen species (ROS) scavenging capabilities. D-AuHNRs@CeO 2 exhibited chiral-selective bioactivity, which preferentially entered damaged L929 mouse fibroblasts cells under oxidative stress, scavenged intracellular ROS, and enhanced wound healing by upregulating Catalase (CAT), transforming growth factor-beta 1 (TGF-β1) in L929 cells, and matrix metalloproteinase-1 (MMP1) in human umbilical vein endothelial cells (HUVECs). Additionally, it effectively shifted RAW264.7 mouse macrophages from the pro-inflammatory M1 phenotype to the pro-repair M2 phenotype, fostering an anti-inflammatory, pro-repair immune microenvironment. Compared with L- and DL- counterparts, D-AuHNRs@CeO 2 showed superior antibacterial and intracellular antioxidant performance. In a mouse model of infected wounds, D-AuHNRs@CeO 2 markedly accelerated wound healing and reduced local bacterial burden, highlighting its multifunctional synergistic therapeutic potential. This work presents a novel nanoplatform for the effective management of infected wounds. Statement of Significance Wound healing is often hindered by a vicious cycle of bacterial infection, excessive inflammation, and oxidative stress. Here, chiral gold helical nanorods decorated with regenerative CeO 2 (AuHNRs@CeO 2 ) was developed. This platform leverages stereoselective interactions to enhance bacterial targeting, converts near-infrared light into heat for photothermal sterilization, and scavenges pathological reactive oxygen species to relieve oxidative stress and inflammation. By integrating multiple therapeutic modalities into one system, this work directly tackles the complex challenge of bacterial wound infection and the subsequent oxidative stress.