Integrated in silico and in vitro evaluation of Camellia sinensis phytosomes in estrogen receptor-positive breast cancer

Endocrine therapy has improved outcomes in estrogen receptor-positive breast cancer (ERPBC), but resistance and relapse remain common. Camellia sinensis contains polyphenols with reported anticancer effects, but their key targets, systems-level mechanisms and optimised delivery for ERPBC are not well defined. Ethanolic leaf extract of Camellia sinensis was profiled by HR-LCMS/MS, and 11 abundant phytocompounds were taken forward for network pharmacology analysis against ERPBC targets. Hub genes and pathways were validated by molecular docking and 200 ns molecular dynamics simulations, focusing on Theacitrin C–CTNNB1 and Plathymenin–ESR1 complexes. A phospholipid phytosome of the extract was then formulated and characterised for particle size, zeta potential and morphology, followed by in vitro cytotoxicity on MCF-7 and L929 cells using the MTT assay. 36 overlapping targets and 8 hub genes were identified. Theacitrin C and Plathymenin showed strong, dynamically stable binding to CTNNB1 and ESR1. The phytosome exhibited a mean size of 519 nm, zeta potential of − 23.0 ± 1.1 mV and mainly spherical particles. It was highly biocompatible toward L929 cells (84.31% viability at 1000 µg/mL) and showed dose-dependent cytotoxicity in MCF-7 cells (IC₅₀ 445.55 µg/mL). Camellia sinensis-derived phytochemicals, particularly Theacitrin C and Plathymenin, appear to modulate CTNNB1- and ESR1-centred networks in ERPBC, and their phytosomal delivery offers a stable, selectively cytotoxic formulation. These findings justify further preclinical evaluation of Camellia sinensis phytosomes as multi-target adjuncts for ERPBC.