Postoperative complications such as tumor recurrence, wound infections, and delayed tissue regeneration persist as critical challenges in melanoma management. In this study, we designed a temperature-tunable photothermal immunotherapy hydrogel dressing (Pd/JQ1@SerMA) to overcome these melanoma postoperative complications. Specifically, this immunomodulatory dressing is composed of methacrylic anhydride-modified sericin (SerMA), palladium nanosheets (Pd) with excellent photothermal performance, and the small-molecule BRD4 inhibitor JQ1. The Pd/JQ1@SerMA hydrogel induces immunogenic cell death (ICD) in tumor cells via high-temperature photothermal effects (> 48 °C), while the released JQ1 downregulates interferon-γ-induced programmed death ligand 1 (PD-L1) expression, thereby mitigating acquired immune resistance and enhancing antitumor immunity. The transcriptomic profiling revealed significant activation of tumor-specific immune pathways, including lymphocyte differentiation, T-cell activation, and systemic immune responses. In addition, the high-temperature photothermal effects (> 48 °C) eliminates over 95% of Staphylococcus aureus and Escherichia coli. Notably, the hydrogel adaptively fills irregular wound defects, and accelerates postoperative tissue regeneration under mild photothermal stimulation (~ 42 °C). In conclusion, this temperature-tunable photothermal immunotherapeutic hydrogel exhibits remarkable clinical potential for preventing tumor recurrence, combating infection, and promoting wound healing.
Tan et al. (Tue,) studied this question.