Hierarchical drug-releasing nanocomposite hydrogel for postoperative synergistic chemo-photothermal therapy of uveal melanoma.

Postoperative recurrence and metastasis remain critical obstacles in uveal melanoma treatment. Herein, we report the synthesis of a hierarchical drug-releasing nanocomposite hydrogel (LAP NPs/ICG gel) via in situ crosslinking of chitosan, co-encapsulating indocyanine green and hyaluronic acid-based lapatinib-loaded nanoparticles (LAP NPs) for postoperative synergistic chemo-photothermal therapy of uveal melanoma. The LAP NPs/ICG gel can be injected into the tumor resection cavity and remains in vivo for more than four weeks. Under near-infrared irradiation, the hydrogel induces rapid local hyperthermia to ablate residual tumor tissue. Concurrently, progressive hydrogel degradation enables sustained release of LAP NPs, which actively target disseminated malignant lesions, enhance tumor penetration and intratumoral retention, ultimately triggering glutathione-responsive intracellular drug release for efficient tumor eradication. In vitro and in vivo studies using MuM-2B tumor models demonstrate that a single local injection of the LAP NPs/ICG gel significantly suppresses tumor growth, postoperative recurrence, and hepatic metastasis. Moreover, the hydrogel-based therapeutic system shows no detectable damage to adjacent healthy tissues or major organs, ensuring a favorable in vivo safety profile. Overall, this multimodal hydrogel system represents a promising adjunctive strategy for postoperative uveal melanoma therapy.