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posted on 2023-04-03, 14:46 authored by Karem A. Court, Hiroto Hatakeyama, Sherry Y. Wu, Mangala S. Lingegowda, Cristian Rodríguez-Aguayo, Gabriel López-Berestein, Lee Ju-Seog, Carlos Rinaldi, Eduardo J. Juan, Anil K. Sood, Madeline Torres-Lugo Particle characterization. (A) Specific Absorption Rate (SAR) values as a function of magnetic field intensity. Particles were heated from 25 to 800 ºC in air using a TA Instruments 2950. Specific absorption rate (SAR) was determined from the heat balance equation using a particle concentration of approximately 1.6mg core/ml suspended in water. The magnetic field was increased and applied for 200s in an Easy Heat ( Ambrell). The temperature was measured with a Luxtron Fluorometric Thermoprobe (LumaSense Technology). (B) Particle size distribution as determiend by dynamic light scattering. Particle hydrodynamic diameter was measured with particles suspended in deionized water at a concentration of 0.01 mg/ml in a Brookhaven Instruments BI-90 Plus Particle Size Analyzer (Holtsville, NY, USA). A thermo-gravimetric analysis was performed to determine the amount of CMDx attached to the magnetic core of the nanoparticles.
Funding
NIH
PR Institute for Functional Nanomaterials
Nanotechnology Center for Biomedical, Environmental and Sustainability Applications
Ovarian Cancer Research Fund
Cancer Prevention and Research Institute of Texas training
History
ARTICLE ABSTRACT
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966–76. ©2017 AACR.
