Self-Amplified Apoptosis Targeting Nanoplatform for Synergistic Magnetic-Thermal/Chemo Therapy In Vivo.

Abstract

The low efficiency homing of nanomaterials in tumors remains a major challenge in nanomedicine. Inspired by the apoptosis targeting properties of phosphatidylserine (PS), a self-amplified apoptosis targeting nanoplatform (MNPs-ZnDPA/β-Lap) is fabricated combining Zn_0.4 Co_0.6 Fe₂ O₄ @Zn_0.4 Mn_0.6 Fe₂ O₄ nanoparticles (MNPs) with an excellent magnetic hyperthermia effect, a chemotherapeutic drug of β-lapachone (β-Lap) with the promotion of cell apoptosis, and the good apoptosis targeting moiety of Zn(II)-bis(dipicolylamine) (bis-ZnDPA) for PS. In an apoptotic 4T1 xenograft model, MNPs-ZnDPA/β-Lap can first accumulate in tumors by the EPR effect. The released β-Lap triggers the apoptosis of cancer cells in the tumor and increases the apoptotic target, which results in amplifying their apoptosis targeting properties. This self-amplified apoptosis targeting efficiency of MNPs-ZnDPA/β-Lap almost inhibits the growth of tumors with the synergistic magnetic-thermal/chemo therapy, which can offer a significant promise for targeting cancer theranostics.