Eduardo Juan

Development of handheld induction heaters for magnetic fluid hyperthermia applications and in-vitro evaluation on ovarian and prostate cancer cell lines

Abstract Objective: Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C–47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge. The AMFs from current and prospective MFH applicators cover relatively large areas; being not suitable for patients having metallic implants near the treatment area. Thus, there will be a clinical need for smaller magnetic field applicators. To this end, a laparoscopic induction heater (LIH) and a transrectal induction heater (TRIH) were developed. Methods: Miniature ‘pancake’ coils were wound and inserted into 3D printed enclosures. Ovarian (SKOV-3, A2780) and prostate (PC-3, LNCaP) cancer cell lines were used to evaluate the instruments’ capabilities in killing cancer cells in vitro, using Synomag®-D nanoparticles as the heat mediators. NIH3T3 normal cell lines were also used with both devices to observe if these cells tolerated the conditions applied. Results: Magnetic field intensities reached by the LIH and TRIH were 42.6 kA m−1 at 326 kHz and 26.3 kA m−1 at 303 kHz, respectively. Temperatures reached in the samples were 41 °C by the LIH and 43 °C by the TRIH. Both instruments successfully accomplished killing cancer cells, with minimal effects on normal cells. Conclusion: This work presents the first line of handheld medical induction heaters and have the potential to be a complement to existing cancer therapies. Significance: These instruments could enable the development of MFH modalities that will facilitate the clinical translation of this thermal treatment.

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

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. 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. The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity 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. 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.