2025
nanotoday

Redox-driven mechanoregulation of invasive TNBC cells using poly(tannic acid) nanospheres

Authors:

Minhee Ku, Suhui Jeong, Nara Yoon, Hwain Myeong, Jinwon Kwon, Jaemoon Yang, Sungbaek Seo

Keywords:

Antioxidant; Mechanoregulation; Polyphenol nanoparticles; Redox signalling; Metastatic cancer cells

Abstract:

Poly(tannic acid) (pTA) nanospheres, assembled from natural tannic acid molecules, exhibit strong intracellular antioxidant activity and effectively modulate the invasive behaviour of triple-negative breast cancer (TNBC) cells. Acting as redox-active nanostructures, pTA nanospheres suppress proliferation and induce mechanoregulatory changes, including altered nuclear morphology, cytoskeletal disassembly, and diminished cell polarity. Specifically, pTA treatment causes spatial mislocalization of MT1-MMP from the invasive front to the perinuclear zone, disrupting its colocalization with F-actin and reducing its matrix-degrading capacity. High-resolution STED and TEM imaging reveal vimentin network collapse and mitochondrial redistribution along microtubules. Metabolic profiling shows a marked decline in oxidative phosphorylation-linked ATP production. Despite these functional disruptions, cleaved caspase-3 remains undetectable, indicating a non-apoptotic, cytostatic state accompanied by autophagy and redox signalling compensation. These findings demonstrate that pTA nanospheres exert redox-driven mechanoregulation in TNBC cells, limiting their invasive potential without inducing cell death, and highlight their promise as a non-lethal nanotherapeutics approach for post-surgical or adjuvant control of metastatic progression.