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

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 MoS₂ 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.