Combination Therapeutic Effect of Psoralen and Paclitaxel-Loaded Superparamagnetic Iron Oxide Nanoparticles for the Treatment of Triple-Negative Breast Cancer

Abstract

Purpose To overcome dose-limiting toxicity and paclitaxel (PTX) resistance in triple-negative breast cancer (TNBC) therapy, as well as the asynchronous in vivo biodistribution of PTX and psoralen (PSO) combination regimens, we developed a highly biocompatible, magnetically targeted nano-co-delivery system. Methods Paclitaxel/psoralen-loaded magnetic composite nanoparticles (P/P-TCNs) were fabricated via nanoprecipitation. The nanocarriers comprise a poly(lactic-co-glycolic acid) (PLGA) core co-encapsulating both therapeutic agents and superparamagnetic iron oxide nanoparticles (SPIONs), shielded by a stabilizing outer phospholipid layer. Results Physiochemically, P/P-TCNs exhibited uniform nanoscale dimensions, a negative surface charge, robust superparamagnetism, and synchronized drug release profiles. In vitro, P/P-TCNs significantly enhanced intracellular drug accumulation in 4T1 murine breast cancer cells, inducing profound G2/M cell cycle arrest and augmented apoptotic response. In vivo live imaging of tumor-bearing mice revealed that under an external magnetic field, P/P-TCNs selectively and efficiently accumulated at the tumor site via tail vein injection. This magnetically guided co-delivery achieved a potent tumor inhibition rate of >85%, significantly outperforming both the free drug combination and non-targeted nanoparticle controls. Furthermore, the nanoplatform demonstrated excellent hemocompatibility (<5% hemolysis) and negligible systemic toxicity in major organs. Conclusion P/P-TCNs facilitate the synchronized, safe, and highly efficient co-delivery of PTX and PSO. By maximizing nanocarrier‑facilitated combinatorial anti-TNBC efficacy while minimizing off-target toxicity, this biocompatible magnetic nanoplatform represents a promising translational strategy for the clinical management of refractory TNBC.