Aggregation-Induced-Emission Luminogens Functionalized MXene Nanosheets for Stimuli-Responsive Hydrogel in Pyroptosis-Mediated Choroidal Melanoma Therapy

Choroidal melanoma is a prevalent intraocular malignant tumor with high mortality rate and liver metastases, related to the lack of sensitive and noninvasive therapeutic modalities. To address the imaging diagnostics and therapeutic predicaments for choroidal melanoma, a novel nanoplatform is developed through the integration of an aggregation-induced emission photosensitizer with two-dimensional MXene nanosheets (MX@PEG-MeoTTPy). This nanoplatform simultaneously exhibits distinctive properties and multiple functions including exceptional biocompatibility, efficient type I reactive oxygen species generation, high-quality fluorescence bioimaging, mild near-infrared (NIR) photothermal performance and superior cellular uptake. Furthermore, a thermosensitive hydrogel composite is engineered to encapsulate the nanosheets, enabling controlled and sustained release over 72 h via NIR irradiation and tumor microenvironment-induced gel-sol transition. The nanoplatform leverages synergistic mild photothermal therapy and photodynamic therapy, leading to precise and sustained tumor ablation through pyroptosis-mediated cell death. Both in vitro and in vivo studies validate that the nanosystem serves as an effective theranostic agent for dual-modal imaging-guided synergistic therapy, offering a multifaceted therapeutic strategy for intraocular tumors and showing significant potential for clinical application in choroidal melanoma therapy.