mNP hyperthermia and hypofractionated radiation activate similar immunogenetic and cytotoxic pathways.

Objective: The goal of this study is to better understand the immunogenetic expression and related cytotoxic responses of moderate but clinically relevant doses of hypofractionated radiation (1x15 Gy and 3x8 Gy) and magnetic nanoparticle hyperthermia (mNPH, CEM43 30).

Methods: Genetic, protein, immunopathology and tumor growth delay assessments were used to determine the immune and cytotoxic responses following radiation and mNPH alone and in combination. Although the thermal dose used, 43 C°/30 min (CEM43 30), typically results in modest independent cytotoxicity, it has shown the ability to stimulate an immune response and enhance other cancer treatments.

In Vitro and In Vivo Delivery of Magnetic Nanoparticle Hyperthermia using a Custom-Built Delivery System.

Hyperthermia has long been used in the treatment of cancer. Techniques have varied from the intra-tumoral insertion of hot iron rods, to systemically delivered tumor antibody-targeted magnetic nanoparticles, at temperatures from 39 ˚C (fever-level) to 1,000 ˚C (electrocautery) and treatment times from seconds to hours. The temperature-time relationship (thermal dose) dictates the effect with high thermal doses resulting in the tissue ablation and lower thermal doses resulting in sublethal effects such as increased blood flow, accumulation of drugs and immune stimulation.

Microfluidic enrichment of bacteria coupled to contact-free lysis on a magnetic polymer surface for downstream molecular detection.

We report on a microsystem that couples high-throughput bacterial immunomagnetic capture to contact-free cell lysis using an alternating current magnetic field (AMF) to enable downstream molecular characterization of bacterial nucleic acids. Traditional methods for cell lysis rely on either dilutive chemical methods, expensive biological reagents, or imprecise physical methods. We present a microchip with a magnetic polymer substrate (Mag-Polymer microchip), which enables highly controlled, on-chip heating of biological targets following exposure to an AMF.

Immunogenetic effects of low dose (CEM43 30) magnetic nanoparticle hyperthermia and radiation in melanoma cells.

In this in vitro study we have used an RNA quantification technique, nanoString, and a conventional protein analysis technique (Western Blot) to assess the genetic and protein expression of B16 murine melanoma cells following a modest magnetic nanoparticle hyperthermia (mNPH) dose equivalent to 30 minutes @ 43°C (CEM43 30) and/or a clinically relevant 8 Gy radiation dose. Melanoma cells with mNPs(2.5 μg Fe/106 cells) were pelleted and exposed to an alternating magnetic field (AMF) to generate the targeted thermal dose.

Hypo-fractionated Radiation, Magnetic Nanoparticle Hyperthermia and a Viral Immunotherapy Treatment of Spontaneous Canine Cancer.

It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia.

Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy.

Background: Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment, involving delivering magnetic nanoparticles (MNPs) into tumours then activating them using an alternating magnetic field (AMF). The system produces not only a magnetic field, but also an electric field which penetrates normal tissue and induces eddy currents, resulting in unwanted heating of normal tissues. Magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field.