Nanocomposite cascading sequential treatment hydrogel patch for postoperative tumor elimination, immune regulation and tissue regeneration after melanoma surgery

To address postoperative melanoma issues of high recurrence and poor wound healing, we developed a nanocomposite hydrogel wound patch (M_xNd/yCe@M SAC) for cascade sequential therapy. Methotrexate (MTX) loaded Nd/Ce-doped mesoporous bioactive glass was encapsulated in a sulfobetaine-polyacrylamide-carboxymethyl chitosan hydrogel via thermal polymerization. Under the acidic microenvironment of the residual tumor, the amide bonds in M_xNd/yCe@M SAC are broken, releasing M_xNd/yCe@M. M_xNd/yCe@M targets tumor cells, and the combined therapy of mild photothermal treatment and chemotherapy ablates tumor cells. Subsequently, the continuously released MTX down-regulates the expression of pro-inflammatory factors and reshapes the immune microenvironment. Finally, M_xNd/yCe@M disintegrates, releasing Si⁴⁺, Ca²⁺, P⁵⁺ and Ce³⁺ ions, which can effectively promote angiogenesis and tissue repair. In the postoperative melanoma model, this method effectively cleared the residual tumors after surgery, shortened the inflammatory period, and promoted tissue regeneration. In conclusion, the nanocomposite hydrogel wound patch for cascade sequential treatment prepared in this study has excellent anti-tumor, immune regulation and tissue repair properties, providing prospective insights for the postoperative treatment of malignant melanoma.