Cyanine5.5 Modified Hyaluronic Acid: Accelerate Infected Wound Healing via Photothermal Therapy, Photodynamic Therapy, and Enzyme‐Like Activities

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Abstract The presence of bacterial drug resistance and biofilms significantly hinders the healing of bacteria‐infected wounds by reducing the effectiveness of antibiotics and maintaining inflammatory reactions. To address this issue, a multifunctional hydrogel (HXM) that combines photothermal therapy (PTT), photodynamic therapy (PDT), and enzyme‐like activity is fabricated in this study. The HXM hydrogel is synthesized via a thiol‐ene click reaction between 4‐ARM‐PEG5000‐SH and hyaluronic acid (HA) modified with organic small molecule dyes (cyanine dyes (Cy5.5 (COOH) )) and methacrylic anhydride (MA) (HA‐Cy5.5 (COOH) ‐MA), followed by MoS 2 coordination. Under near‐infrared irradiation, the hydrogel exerts potent antibacterial effects via synergistic PTT/PDT. After infection control, the hydrogel promotes the polarization of macrophages to the M2 type, upregulating antioxidant enzymes (superoxide dismutase‐like) to scavenge excess reactive oxygen species (ROS). Meanwhile, it secretes anti‐inflammatory cytokine interleukin‐10, which helps resolve inflammation and accelerate infected wound repair. Further, its intrinsic catalase‐like activity degrades ROS, disrupting the ROS cycle. In vivo, the HXM hydrogel exhibited antibacterial, antioxidant, and anti‐inflammatory functions, enhancing wound closure through coordinated biofilm disruption and oxidative stress mitigation. Therefore, this work is expected to provide a potential therapeutic strategy for promoting infected wound healing in vivo.

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