Synergistic anti-Triple Negative Breast Cancer Study with Paclitaxel/Berberine Nanoparticle Co-Delivery System

Chemoresistance remains a major barrier to the effective treatment of triple-negative breast cancer (TNBC). To enhance the targeting and chemosensitivity of paclitaxel (PTX) for TNBC treatment, we developed a dual-drug-loaded nanodelivery system (BBR@PTX NPs) using BI-PEG-PTX polymer as the carrier, with berberine (BBR) loaded at an optimal ratio (PTX:BBR =1:10) determined by synergistic toxicity assays. The BBR@PTX NPs in this study demonstrated loading efficiencies of 9.5% for PTX and 28.06% for BBR, with an average particle size of 130-150 nm and a uniform distribution. In in vitro cellular assays, BBR potentiates PTX, achieving synergistic anti-tumor efficacy. The BBR@PTX NP co-delivery system enhances bioavailability by evading macrophage phagocytosis and lysosomal capture. The ability to inhibit cell growth, metastasis, and induce apoptosis was significantly enhanced after the NPs were taken up by tumor cells. In vivo experiments demonstrated that the BBR@PTX NP nanomicellar system enhanced tumor targeting, anti-tumor activity, and biosafety compared to single-agent formulations. These findings establish an effective approach to develop high-performance, selective, and low-toxicity nanocellular aggregates for combined therapy of solid triple-negative breast cancer.