Multifunctional Magnetic Nanoplatform Eliminates Cancer Stem Cells via Inhibiting the Secretion of Extracellular Heat Shock Protein 90

Abstract

Cancer stem cells (CSCs) are responsible for malignant tumor initiation, recurrences, and metastasis. Therefore, targeting CSCs is a promising strategy for the development of cancer therapies. A big challenge for CSC-based cancer therapy is the overexpression of therapeutic stress protein, heat shock protein 90 (Hsp90), which protects CSCs from further therapeutic-induced damage, leading to the failure of treatment. Thus, efficient strategies to target CSCs are urgently needed for cancer therapy. To this end, a multifunctional nanoparticle (MNP) for CSC-based combined thermotherapy and chemotherapy is reported. This strategy dramatically suppresses tumor growth in breast CSC xenograft-bearing mice. Furthermore, a new mechanism is present that the MNP exerts its striking effects on CSCs by inhibiting the secretion of extracellular Hsp90 (eHsp90), resulting in the interruption of several key signaling pathways. These findings open new perspectives on the use of an MNP for effective CSC-based cancer treatment by inhibiting the function of eHsp90.

Keywords: cancer stem cells; extracellular heat shock protein 90; multifunctional nanoparticles; signaling pathways; thermotherapy and chemotherapy.