Superparamagnetic core-shell nanoparticles enable co-delivery of psoralen and paclitaxel for the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) therapy with paclitaxel (PTX) is hampered by systemic toxicity, drug resistance, and poor delivery efficiency when combined with psoralen (PSO). In this study, paclitaxel/psoralen-loaded magnetic composite nanoparticles (P/P-TCNs) were fabricated via an oil-in-water (O/W) emulsion method, modified with an outer phospholipid layer for stability. Physicochemical properties, drug release, in vitro cellular uptake, apoptosis, cell cycle arrest, and in vivo biodistribution, antitumor efficacy, and biosafety were systematically evaluated. P/P-TCNs exhibited small size, uniform dispersion, negative zeta potential, and superparamagnetism. In vitro, they enhanced cellular uptake, induced apoptosis, and arrested TNBC cells at G2/M phase. In tumor-bearing nude mice, P/P-TCNs accumulated efficiently in tumors, achieving >85% tumor inhibition (superior to free drug combinations/control nanoparticles) with hemolysis rate < 5% and no obvious organ toxicity. Collectively, P/P-TCNs enable synergistic PTX/PSO delivery, potentiating anti-TNBC efficacy with excellent biocompatibility, providing a safe and efficient nanotherapeutic strategy.