Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-FeO with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (<250 Oe). This may extend MNP hyperthermia therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue.

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The unique properties of magnetic nanoparticles (MNPs), coupled with versatile surface engineering techniques, have led to a rising class of screening methods that enable separation of specific cell populations from complex biological samples. The growing sophistication and efficiency of these methods have far reaching implications for both fundamental research and clinical applications. In this study, the synthesis and surface engineering of MNPs is reviewed. Here, a model is introduced to illustrate how MNP morphology and particle–particle interactions influence magnetization, which is a key consideration in designing and selecting MNPs for efficient cell separations. Building upon these themes, immunomagnetic assays for capturing, isolating, and characterizing rare cell types from complex biological mixtures are reviewed. Although the focus of this study is on circulating tumor cells, these same techniques can be applied in screening for other rare cells of interest, such as various stem cell populations. In conclusion, current challenges and future directions for magnetic ‐nanomaterial‐based cell screening systems are discussed.

This paper describes the synthesis and properties of a new type of magnetic nanoparticle (MNP) for use in the hyperthermia treatment of tumors. These particles consist of 2–4 nm crystals of gamma-Fe2O3 gathered in 20–40 nm aggregates with a coating of carboxymethyl-dextran, producing a zetasize of 110–120 nm. Despite their very low saturation magnetization (1.5–6.5 emu/g), the specific absorption rate (SAR) of the nanoparticles is 22–200 W/g at applied alternating magnetic field (AMF) with strengths of 100–500 Oe at a frequency of 160 kHz.

Iron magnetic nanoparticles were synthesized under an inert atmosphere via the reaction between FeCl3 and NaBH4 in droplets of water in a microemulsion consisting of octane with cetyl trimethylammonium bromide and butanol as surfactants. A thin Fe3O4 layer was produced on the iron nanoparticles using slow, controlled oxidation at room temperature. A silica shell was deposited on the Fe3O4 using 3-aminopropyltrimethoxysilane following the method of Zhang et al. [Mater. Sci. Eng. C 30 (2010) 92–97]. The structure and chemistry of the resulting nanoparticles were studied using variety of methods and their magnetic properties were determined. The diameter of the iron core was typically 8–16 nm, while the thickness of the Fe3O4 shell was 2–3 nm. The presence of the silica layer was confirmed using Fourier transform infra-red spectroscopy and the number of NH2-groups on each nanoparticle was determined based on colorimetric tests using ortho-phthalaldehyde.

Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm nanoparticles exhibited lower in vitro targeting efficiency when compared to those built with commercially sourced 180 nm nanoparticles. In vivo, however, the two Ffab-IONP platforms achieved equivalent tumor homing, although the smaller 120 nm IONPs were more prone to liver sequestration. Overall, the results show that Ffab-mediated targeting of IONPs yields specific, high-level accumulation within cancer cells, and this fact suggests that Ffab-IONPs could have future utility in ovarian cancer diagnostics and therapy.

The use of magnetic nanoparticles (mNP’s) to induce local hyperthermia has been emerging in recent years as a promising cancer therapy, in both a stand-alone and combination treatment setting. Studies have shown that cancer cells associate with, internalize, and aggregate mNP’s more preferentially than normal cells. Once the mNP’s are delivered inside the cells, a low frequency (30 kHz–300 kHz) alternating electromagnetic field is used to activate the mNP’s. The nanoparticles absorb the applied field and provide localized heat generation at nano-micron scales. It has been shown experimentally that mNP’s exhibit collective behavior when in close proximity. Although most prevailing mNP heating models assume there is no magnetic interaction between particles, our data suggests that magnetic interaction effects due to mNP aggregation are often significant; In the case of multi-crystal core particles, interaction is guaranteed. To understand the physical phenomena responsible for this effect, we modeled electromagnetic coupling between mNP’s in detail. The computational results are validated using data from the literature as well as measurements obtained in our lab. The computational model presented here is based on a method of moments technique and is used to calculate magnetic field distributions on the nanometer scale, both inside and outside the mNP.

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