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

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.