Inflammation-reducing thermosensitive hydrogel with photothermal conversion for skin cancer therapy

Photothermal therapy (PTT) has widely been utilized for postoperative treatment of skin cancer, while high temperature, usually >50 °C, would induce damage to healthy tissue and increased wound inflammation. Herein, we developed an "all in one" hydrogel to enhance mild PTT for postoperative skin cancer treatment while circumventing photothermo-induced inflammation by loading quercetin (Que)-coated tannin‑iron (TA-Fe) nanoparticles with poly (N-acrylylglycine) amine (PNAGA) hydrogel (Que@TA-Fe@PNAGA). Exposure to near-infrared light, Que.@TA-Fe@PNAGA occurred a mild temperature increase (∼47 °C), which induces local mild PTT and disrupts the hydrogen bonds within the hydrogel, triggering a gel-to-sol phase transition and the release of Que.@TA-Fe nanoparticles. These released nanoparticles inhibit the expression of heat shock proteins in tumor cells by producing reactive oxygen species and enter inflammatory cells to release TA and Que. via acid hydrolysis, reducing tumor necrosis factor-α expression by 66.6 % and promoting M1-to-M2 macrophage conversion. Based on this integrated functionality, Que.@TA-Fe@PNAGA hydrogel achieves over 99.4 % tumor inhibition rate, effectively avoids photothermo-induced damage in normal tissue and inflammation, and thus represents a new approach for postoperative photothermal therapy in skin cancer treatment.