A multifunctional magnetic nanosystem based on 'two strikes' effect for synergistic anticancer therapy in triple-negative breast cancer

摘要

Multifunctional magnetic nanoparticles (MNPs) were widely used for ablation of cancer cells because of their potential on physical treatment. Herein, we developed the "cell targeting destructive" multifunctional polymeric nanoparticles (named as HA-Olb-PPMNPs) based on PEI-PLGA co-loaded with the anticancer drug Olaparib (Olb) and superparamagnetic iron oxide nanoparticles (Fe3O4 NPs), and further coated with a low molecular weight hyaluronic acid (HA) on its surface. Due to the high affinity between HA and CD44-receptor on cell surface of triple negative breast cancer (TNBC), an active targeting can be achieved. Under a rotating magnetic field (RMF), HA-Olb-PPMNPs produced a physical transfer of mechanical force by incomplete rotation. This mechanical force could cause the "two strikes" effect on the cells, in which "First-strike" was to damage the cell membrane structure (magneto-cell-lysis), another "Second-strike" could activate the lysosome-mitochondrial pathway by injuring lysosomes to induce cell apoptosis (magneto-cell-apoptosis). Therefore, the mechanical force and Olb exert dual anti-tumor effect to achieve synergistic therapeutic in the presence of RMF. This study proposes a novel multi-therapeutic concept for TNBC, as well as provided evidences of new anti-tumor therapeutic effects induced by the magnetic nanoparticles drug system.