Self-assembled nanoparticles of epigallocatechin gallate and tannic acid nanoparticles against triple-negative breast cancer via mediating mitochondrial damage

Breast cancer continues to be the most common cancer affecting women globally, with triple-negative breast cancer (TNBC) emerging as a particularly challenging subtype due to its high invasiveness and unfavorable prognosis. While chemotherapy remains the standard treatment for TNBC, patients often face significant side effects and the potential for drug resistance, which can complicate treatment outcomes. In this study, we focused on the in vitro evaluation of a novel nanotherapeutic strategy for TNBC. Epigallocatechin gallate (EGCG), a major catechin derived from green tea, has demonstrated anti-cancer potential, but its clinical application is hindered by low bioavailability and instability. To address these limitations, we developed self-assembled nanoparticles composed of EGCG and tannic acid (TA), stabilized by appropriate excipients, to form EGCG-TA nanoparticles (ET-NPs). The rationale for combining EGCG with TA is based on their complementary polyphenolic structures and potential synergistic anti-tumor mechanisms, as supported by combination index (CI) and IC50 data. Characterization of these nanoparticles demonstrated their favorable physicochemical properties, including optimal particle size, zeta potential, and stability. In vitro studies showed that ET-NPs exhibited improved serum stability and significantly greater inhibition of TNBC cells proliferation compared to free EGCG or TA. The observed anti-tumor effect is linked to a significant reduction in mitochondrial membrane potential and increased intracellular reactive oxygen species (ROS) levels, ultimately resulting in mitochondrial damage and cell death. Additionally, FTIR analysis confirmed the successful assembly of EGCG and TA through non-covalent interactions. By improving the stability and anti-tumor properties of EGCG, the self-assembled ET-NPs represent a promising new approach for the in vitro treatment of TNBC, providing a foundation for future in vivo and translational studies.