<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Abstract

Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity ® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.

Potential anti-tumor activity of 13.56 MHz alternating magnetic hyperthermia and chemotherapy on the induction of apoptosis in human colon cancer cell lines HT29 and HCT116 by up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins

“…5 and 6). The results indicated that magnetic hyperthermia improved the efficacy of chemotherapy, which could be due to the constructive effect of hyperthermia on the permeability of the cell membrane to the chemotherapeutic agents (Mérida et al 2020). The combinational treatment of MNPs and AMF hyperthermia resulted in more cytotoxicity than MNPs, and AMF alone (P < 0.05, Figs.…”

Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles

“…First proposed by therapeutically by Gilchrist [281] in the 1950s, iron oxide nanoparticles provide localized heat sources for destroying diseased tissue [282] or dispersal of biofilms [283,284]. SPIONs in particular generate a significant amount of heat under an applied magnetic field (42-45 °C) [285] and have been used for cancer treatment through magnetic hyperthermia [286][287][288][289][290]. Taratula [291] recently developed magnetic nanoclusters composed of cobalt-and manganese-doped hexagonal iron oxide nanoparticles encapsulated in PEG-based polymer nanocarriers for hyperthermia treatment of ovarian cancer (Fig.…”

Magnetic mediators for ultrasound theranostics

“…DOX-Fe 3 O 4 -TSL significantly inhibited tumor growth while causing no significant damage to normal tissues under NIR laser irradiation 101 . The combination of sonoporation and MH was proposed by Merida et al 102 . The authors used iron oxide NPs to induce MH and low-intensity US to enhance intracellular delivery during sonoporation.…”