Cancer therapy with iron oxide nanoparticles: Agents of thermal and immune therapies.

Significant research and preclinical investment in cancer nanomedicine has produced several products, which have improved cancer care. Nevertheless, there exists a perception that cancer nanomedicine 'has not lived up to its promise' because the number of approved products and their clinical performance are modest. Many of these analyses do not consider the long clinical history and many clinical products developed from iron oxide nanoparticles. Iron oxide nanoparticles have enjoyed clinical use for about nine decades demonstrating safety, and considerable clinical utility and versatility. FDA-approved applications of iron oxide nanoparticles include cancer diagnosis, cancer hyperthermia therapy, and iron deficiency anemia. For cancer nanomedicine, this wealth of clinical experience is invaluable to provide key lessons and highlight pitfalls in the pursuit of nanotechnology-based cancer therapeutics. We review the clinical experience with systemic liposomal drug delivery and parenteral therapy of iron deficiency anemia (IDA) with iron oxide nanoparticles. We note that the clinical success of injectable iron exploits the inherent interaction between nanoparticles and the (innate) immune system, which designers of liposomal drug delivery seek to avoid. Magnetic fluid hyperthermia, a cancer therapy that harnesses magnetic hysteresis heating is approved for treating humans only with iron oxide nanoparticles. Despite its successful demonstration to enhance overall survival in clinical trials, this nanotechnology-based thermal medicine struggles to establish a clinical presence. We review the physical and biological attributes of this approach, and suggest reasons for barriers to its acceptance. Finally, despite the extensive clinical experience with iron oxide nanoparticles new and exciting research points to surprising immune-modulating potential. Recent data demonstrate the interactions between immune cells and iron oxide nanoparticles can induce anti-tumor immune responses. These present new and exciting opportunities to explore additional applications with this venerable technology. Clinical applications of iron oxide nanoparticles present poignant case studies of the opportunities, complexities, and challenges in cancer nanomedicine. They also illustrate the need for revised paradigms and multidisciplinary approaches to develop and translate nanomedicines into clinical cancer care.

Experimental estimation and analysis of variance of the measured loss power of magnetic nanoparticles.

Magnetic nanoparticles dissipate heat when exposed to alternating magnetic fields (AMFs), making them suitable for cancer hyperthermia. Therapeutic heating applications demand accurate characterization of the heating power dissipated by the particles. Specific loss power (SLP) generated by magnetic nanoparticles is estimated from calorimetric heating measurements. Such measurements require adiabatic conditions, yet they are typically performed in an AMF device with non-adiabatic conditions. We have measured heating from four magnetic nanoparticle constructs using a range of frequencies (150-375 kHz) and magnetic fields (4-44 kA/m). We have extended a method developed to estimate SLP from the inherently non-adiabatic measurements, where we identify data ranges that conform to (quasi)-adiabatic conditions. Each time interval of measurement that met a predetermined criterion was used to generate a value of SLP, and the mean from all estimates was selected as the estimated SLP. Despite the application of rigorous selection criteria, measured temperature data displayed variability at specific heating loads resulting in larger variance of calculated mean SLP values. Overall, the results show a linear dependence of the SLP with AMF frequency, as anticipated by current models. Conversely, measured amplitude-dependent SLP profiles of all studied constructs conform to no predictions of current models.

Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

Optimizing bipolar radiofrequency ablation treatment by means of pulsed currents.

Given the high mortality rate, liver cancer is considered to be a difficult cancer to treat. Consequently, alternative strategies are being developed such as radiofrequency ablation (RFA). RFA applies radiofrequent currents leading to local heating of the tumoral tissue. Accurate numerical modeling contributes to a better knowledge of the physical phenomena and allows optimizations. In this work, the bipolar radiofrequency ablation technique is explored followed by an optimization by means of pulsed currents. Numerical results clearly show the larger ablation zones due to the pulsed currents. Hence, pulsed bipolar RFA increases the efficacy and has the potential to be incorporated in clinical practice.