Precision-targeted explosion of biomimetic nanoparticles for the effective treatment of uveal melanoma

Abstract

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults, originating from the melanocytes within the uvea. Currently, the treatment of ocular tumors predominantly relies on conventional approaches such as brachytherapy and enucleation. Despite the limited pharmaceutical treatment options for uveal melanoma (UM), the effectiveness of ocular drug delivery is hindered by the ocular barrier to local drug administration and the complex tumor microenvironment (TME). In response, biomimetic low-density lipoprotein nanoparticles (LD-DPVP NPs) with active targeting capabilities were designed. This nanodrug system combined photosensitizer (verteporfin, VP) with the tumor vascular normalization drug (dexamethasone, DEX) to achieve low-toxicity, high-efficacy treatment of intraocular tumors. After intravenous injection, the nanoparticles selectively targeted the tumor site and induced VP to produce reactive oxygen species (ROS) that killed tumor cells under near-infrared laser stimulation. The produced ROS could also trigger the cleavage of the DEX prodrug (DPD) and rapid release of DEX via breakage of the thioether bond (TK). Additionally, DEX could modulate the TME, improving the delivery of nanoparticles to the tumor and further enhancing the efficacy of LD-DPVP NPs. We believe the biomimetic nanoparticles designed in this study have a potential clinical application value in inhibiting UM growth and provided a promising strategy for addressing other ocular malignancies.