Combined Magnetic Nanoparticle-based MicroRNA and Hyperthermia Therapy to Enhance Apoptosis in Brain Cancer Cells

摘要

In recent years, mild hyperthermia (40–45 °C) has been increasingly investigated as an adjuvant that can effectively sensitize tumors to chemotherapy and radiotherapy as well as induce apoptosis. [ 1 ] In particular, magnetic hyperthermia, wherein the exposure of magnetic nanoparticles (MNPs) to an alternating magnetic fi eld (AMF) results in the induction of hyperthermia via Neel and Brownian relaxation, represents an attractive approach for the selective heating of tumors while sparing surrounding healthy tissues. [ 2 ] However, the treatment of tumors with magnetic hyperthermia results in a number of molecular effects including a sharp increase in the synthesis of heat shock proteins (HSPs), whose fundamental function is to protect cellular proteins from degradation. It has been reported that these effects occur through numerous signaling pathways involved in therapeutic resistance including the activation of DNA repair mechanisms (via the BRCA family) [ 3 ] and the inhibition of apoptosis (via the Akt/PI3K pathway). [ 4,5 ] As such, HSP expression following magnetic hyperthermia signifi cantly hinders MNP-mediated apoptosis in cancer cells. For instance, it has been demonstrated that the activation of HSPs preserves cancer cell viability and can impart cancer cells with resistance to chemotherapy and radiotherapy. [ 6 ]