Transmembrane MUC18, a marker of cancer metastasis, is highly expressed on most human cancers, and its expression level indicates metastasis tendency of the cancers. Herein, we demonstrate that targeting MUC18 with polydopamine nanoparticles (PDA NPs) and a mild photothermal effect can completely cease the migration of melanoma and breast cancer cells. The inhibited cell migration can be attributed to the altered actin cytoskeleton, cell stiffness, and cell morphology, as revealed by nanomechanical and super resolution fluorescence imaging techniques. Further mechanistic studies at the molecular level show that MUC18 targeted PDA NPs and a mild photothermal treatment produce a synergistic effect on the actin cytoskeleton by downregulating the transmembrane MUC18 and interrupting ezrin-radixin-moesin phosphorylation, thereby releasing the actin cytoskeleton from the cell membrane and compromising force transduction through the actin cytoskeleton to the transmembrane MUC18. Overall, this work introduces a safe, effective, and broadly applicable approach to stop cancer cell migration without killing the cancer cells, which represents a radical deviation from the conventional photothermal therapy that requires the ablation of cancer cells using high dose of photo-absorbers and laser irradiation. The concept of targeting transmembrane tumor markers and disrupting their downstream effectors (i.e., actin and actin-binding proteins), opens up a new avenue to cancer therapy, that is, <i>via</i> altering the biophysical properties of the cancer cells and their related migration ability.

Transmembrane MUC18 targeted polydopamine nanoparticles and a mild photothermal effect synergistically disrupt actin cytoskeleton and migration of cancer cells

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.