Highly tumoricidal efficiency of non-oxidized MXene-Ti₃C₂Tx quantum dots on human uveal melanoma

Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti₃C₂Tx quantum dots (NMQDs-Ti₃C₂Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti₃C₂Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti₃C₂Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti₃C₂Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti₃C₂Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.