It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.

The synthesis of well-defined nanoparticle materials has been an area of intense investigation, but size control in nanoparticle syntheses is largely empirical. Here, we introduce a general method for fine size control in the synthesis of nanoparticles by establishing steady state growth conditions through the continuous, controlled addition of precursor, leading to a uniform rate of particle growth. This approach, which we term the "Extended LaMer Mechanism" allows for reproducibility in particle size from batch to batch, as well as the ability to predict nanoparticle size by monitoring the early stages of growth. We have demonstrated this method by applying it to a challenging synthetic system: magnetite nanoparticles. To facilitate this reaction, we have developed a reproducible method for synthesizing an iron oleate precursor that can be used without purification. We then show how such fine size control affects the performance of magnetite nanoparticles in magnetic hyperthermia.

Though the concepts of magnetic fluid hyperthermia (MFH) were originally proposed over 50 years ago, the technique has yet to be successfully translated into routine clinical application. Significant challenges must be addressed if the field is to progress and realise its potential as an option for treatment of diseases such as cancer. These challenges include determining the optimum fields and frequencies that maximise the effectiveness of MFH without significant detrimental off-target effects on healthy tissue, achieving sufficient concentrations of magnetic nanoparticles (MNPs) within the target tumour, and developing a better mechanistic understanding of MNP-mediated energy deposition and its effects on cells and tissue. On the other hand, emerging experimental evidence indicates that local thermal effects indeed occur in the vicinity of energy-dissipating MNPs. These findings point to the opportunity of engineering MNPs for the selective destruction of cells and/or intracellular structures without the need for a macroscopic tissue temperature rise, in what we here call magnetically mediated energy delivery (MagMED).

Magnetic Fluid Hyperthermia (MFH) uses heat generated by magnetic nanoparticles exposed to alternating magnetic fields to cause a temperature increase in tumors to the hyperthermia range (43–47 °C), inducing apoptotic cancer cell death. As with all cancer nanomedicines, one of the most significant challenges with MFH is achieving high nanoparticle accumulation at the tumor site. This motivates development of synthesis strategies that maximize the rate of energy dissipation of iron oxide magnetic nanoparticles, preferable due to their intrinsic biocompatibility. This has led to development of synthesis strategies that, although attractive from the point of view of chemical elegance, may not be suitable for scale-up to quantities necessary for clinical use. On the other hand, to date the aqueous co-precipitation synthesis, which readily yields gram quantities of nanoparticles, has only been reported to yield sufficiently high specific absorption rates after laborious size selective fractionation. This work focuses on improvements to the aqueous co-precipitation of iron oxide nanoparticles to increase the specific absorption rate (SAR), by optimizing synthesis conditions and the subsequent peptization step. Heating efficiencies up to 1,048 W/gFe (36.5 kA/m, 341 kHz; ILP = 2.3 nH·m2·kg−1) were obtained, which represent one of the highest values reported for iron oxide particles synthesized by co-precipitation without size-selective fractionation. Furthermore, particles reached SAR values of up to 719 W/gFe (36.5 kA/m, 341 kHz; ILP = 1.6 nH·m2·kg−1) when in a solid matrix, demonstrating they were capable of significant rates of energy dissipation even when restricted from physical rotation. Reduction in energy dissipation rate due to immobilization has been identified as an obstacle to clinical translation of MFH. Hence, particles obtained with the conditions reported here have great potential for application in nanoscale thermal cancer therapy.

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The use of dynamic magnetic susceptibility measurements is reported to study nanoparticle–protein interactions in situ. The technique consists of measuring the rotational diffusivity of thermally blocked magnetic nanoparticles (MNPs) in protein solutions. To illustrate the technique, the effect of nanoparticle zeta potential in carboxymethyl‐dextran‐coated MNPs and their interaction with model anionic and cationic proteins, such as bovine serum albumin (BSA), immunoglobulin G (IgG), fibrinogen (FIBR), apo‐transferrin (TRANS), lysozyme (LYZ), and histone (HIS), in a range of protein concentrations is studied. Experiments indicate that interactions between the negatively charged particles and the negatively charged proteins BSA, IgG, FIBR, and TRANS are negligible. However, positively charged proteins LYZ and HIS readily absorb onto the nanoparticles, as evidenced by an increase in size and eventual aggregation of the particles. Onset of this effect seems to happen at a lower concentration of HIS compared with LYZ. The technique could be applied to other particle surface coatings and to particles in complex protein mixtures, such as whole blood and serum, allowing systematic in situ studies of nanoparticle–protein interactions.

Objectives To test the hypotheses that (a) the chairside/handheld dental scanner combined with a metrology software will measure clinical wear in vivo in agreement with measurements from X‐ray computed microtomography and; (b) polished monolithic zirconia does not cause accelerated wear of opposing enamel. Materials and methods Thirty single crowns were randomized to receive a monolithic zirconia or metal‐ceramic crown. Two non‐restored opposing teeth in the same quadrants were identified to serve as enamel controls. After cementation, quadrants were scanned using an intraoral dental scanner. Patients were recalled at 6‐months and 1‐year for re‐scanning. Scanned images were compared using a metrology software to determine maximum vertical wear of teeth. The accuracy of the scanning measurements from this new method was compared with X‐ray computed microtomography (micro‐CT) measurements. Statistical analysis was performed using Mann–Whitney U test to determine significant differences between wear of enamel against zirconia, metal‐ceramic or enamel. Linear regression analysis determined agreement between measurements obtained using intraoral scanning and micro‐CT. Results Regression analysis demonstrated that there is a quantitative agreement between depth and volume measurements produced using intraoral scanning and the micro‐CT methodologies. There was no significant difference between the wear of enamel against polished monolithic zirconia crowns and enamel against enamel. Conclusions Intraoral scanning combined with a matching software can accurately quantify clinical wear to verify that monolithic zirconia exhibited comparable wear of enamel compared with metal‐ceramic crowns and control enamel. Agreement between the intraoral scanner and the micro‐CT was 99.8%. Clinical Trials.gov NCT02289781.