Targeted hyperthermia-induced cancer cell death by superparamagnetic iron oxide nanoparticles conjugated to luteinizing hormone-releasing hormone

Abstract

The hyperthermia-induced cytotoxicity of gold-coated SPIONs conjugated to LHRH (SPIONs@Au-LHRH) has been studied in LHRH-receptor overexpressing murine GT1-7 hypothalamic neurons (noncancerous) and human LNCaP cells (cancerous). In the absence of an external magnetic field, SPIONs@Au-LHRH were least cytotoxic to either cell type. When cells were pretreated with SPIONs@Au-LHRH and then exposed to a magnetic field (465 Oe for 15 or 2×15 min), both cell types showed marked decreases in viability and proliferation. The cell death in GT1-7 neurons was found to be late apoptosis or early necrosis, while necrosis was prominent in LNCaP cells. The LNCaP cells exposed to the magnetic field for 15 min showed a significant drop in the mitochondrial transmembrane potential; however, no such change was evident in GT1-7 neurons for the first 15 min. The cell death in LNCaP cells was found to be mediated through the caspase-3-dependent pathway. There was an increased expression of heat shock protein 70 in GT1-7 neurons, and no such increase was seen in LNCaP cells. It is suggested that noncancerous GT1-7 neurons are more resistant to the heat-induced cytotoxicity of SPIONs@Au-LHRH than are LNCaP cells due to increased expression of HSP70. The results show promise toward the selective tumoricidal actions of targeted magnetic nanoparticles.

Keywords

• heat shock proteins
• mitochondrial transmembrane potential
• nanomedicine
• nanoparticles
• role of caspases
• selective tumoricidal activity