Inhibiting Migration of Endothelial-Derived Mesenchymal Cells Using a Nanoparticle-Based Photothermal Treatment Impedes Atherosclerosis and Cancer Progression

The migration and invasion of endothelial-derived mesenchymal cells (EMCs) play a crucial role in both atherosclerotic plaque formation and cancer metastasis. However, current strategies aimed at suppressing EMC formation often suffer from poor specificity and undesirable side effects, and few efforts have directly targeted the migratory and invasive behaviors of EMCs. In this study, we present a nanoparticle-based strategy to specifically inhibit EMC migration and invasion using cadherin-2-targeted melanin nanoparticles in combination with a mild photothermal treatment. Cell migration and invasion assays demonstrate that the synergistic effect of nanoparticle uptake and photothermal treatment effectively impedes the EMC motility. Atomic force and super resolution microscopy indicate that this inhibition is associated with disruption of the actin cytoskeleton and consequent morphological alterations. Furthermore, Western blot analyses elucidate the underlying molecular mechanism, showing that cadherin-2-dependent RhoA activation is downregulated by the combined nanoparticle and photothermal treatment, leading to cytoskeletal disorganization. Overall, these in vitro findings serve as a proof-of-concept study for a potential alternative or complementary strategy to attenuate atherosclerotic plaque development and cancer metastasis by targeting the migration and invasion of EMCs from a mechanistic perspective.