Multi-responsive nanocomposite hydrogel for synergistic photothermal-chemotherapy to prevent postoperative recurrence and metastasis of uveal melanoma

Postoperative recurrence and metastasis remain major challenges in improving the prognosis of uveal melanoma (UM). Herein, we developed a chitosan-based injectable multi-responsive nanocomposite hydrogel (CPT NPs gel) for localized and synergistic photothermal-chemotherapy following tumor resection. This hydrogel co-encapsulates pH/GSH-responsive camptothecin-loaded nanoparticles (CPT NPs) and polydopamine, forming a porous, self-healing network that persists in vivo for over 28 days. Upon near-infrared (NIR) irradiation, the hydrogel rapidly elevates the local temperature to approximately 60 °C within 40 s, enabling efficient ablation of residual tumor tissue at the surgical site. Concurrently, CPT NPs are sustainably released from the hydrogel and enter systemic circulation, where they undergo charge reversal upon encountering the mildly acidic microenvironment of metastatic lesions to enhance cellular uptake and subsequently disassemble in response to intracellular GSH, thereby eliminating disseminated UM cells. In a partially resected MuM-2B tumor-bearing mouse model, CPT NPs gel combined with NIR irradiation completely abrogated local tumor recurrence and significantly reduced pulmonary metastasis, limiting metastatic infiltration to less than 1 % without observable systemic toxicity. Overall, this study presents a promising multifunctional therapeutic platform for the synergistic prevention of UM recurrence and metastasis.