Chiral Titanium Dioxide Nanoparticles Induce Breast Cancer Lung Metastasis

Abstract

ABSTRACT In this study, chiral titanium dioxide nanoparticles (NPs) with a g ‐factor of 0.008 at 930 nm wavelength were fabricated, and their effect on breast cancer metastasis was systematically investigated. Cellular experiments demonstrated that left‐handed titanium dioxide NPs ( L ‐TiO 2 NPs) enter MODE‑K intestinal epithelial cells via toll‑like receptor 4 and trigger the generation of intracellular reactive oxygen species (ROS), which activating the nuclear factor‑κB and NOD‑like receptor thermal protein domain‑associated protein 3 (NLRP3) signaling pathway to drive the release of inflammatory mediators, which subsequently induced epithelial‑mesenchymal transition (EMT) in 4T1‑luc breast cancer cells and remodel the lung microenvironment, significantly enhancing the migration and adhesion of 4T1‑luc cells to 3B‑11 lung endothelial cells, verified in a mouse model of breast cancer, indicating that L ‐TiO 2 NPs not only increased the migratory and invasive capacities of the primary tumor, but also shaped a microenvironment in the lungs that facilitated the colonization of circulating tumor cells (CTCs), thereby driving the acceleration of breast cancer lung metastasis. This work systematically elucidates that chiral TiO 2 NPs regulate the distal microenvironment through the ROS‐inflammatory signaling cascade to accelerate lung metastasis of breast cancer, suggesting that the risk of inducing tumor metastasis should be carefully evaluated when designing chiral nanomedicines.