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.

This article describes a versatile method to fabricate magnetic microstructures with complex two-dimensional geometric shapes using magnetically assembled iron oxide (Fe3O4) and cobalt ferrite (CoFe2O4) nanoparticles. Magnetic pole patterns are imprinted into magnetizable media, onto which magnetic nanoparticles are assembled from a colloidal suspension into defined shapes via the shaped magnetic field gradients. The kinetics of this assembly process are studied by evaluation of the microstructure features (e.g., line width and height) as a function of time, particle type, and volume fraction. After assembly, the iron oxide particles are cross-linked in situ and subsequently released by dissolving a sacrificial layer. The free-floating magnetic structures are shown to retain their patterned shape during manipulation with external magnetic fields.

Iron oxide nanoparticles are of interest in a wide range of biomedical applications due to their response to applied magnetic fields and their unique magnetic properties. Magnetization measurements in constant and time-varying magnetic field are often carried out to quantify key properties of iron oxide nanoparticles. This chapter describes the importance of thorough magnetic characterization of iron oxide nanoparticles intended for use in biomedical applications. A basic introduction to relevant magnetic properties of iron oxide nanoparticles is given, followed by protocols and conditions used for measurement of magnetic properties, along with examples of data obtained from each measurement, and methods of data analysis.

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We report observations of breakdown of the Stokes-Einstein relation for the rotational diffusivity of polymer-grafted spherical nanoparticles in polymer melts. The rotational diffusivity of magnetic nanoparticles coated with poly(ethylene glycol) dispersed in poly(ethylene glycol) melts was determined through dynamic magnetic susceptibility measurements of the collective rotation of the magnetic nanoparticles due to imposed time-varying magnetic torques. These measurements clearly demonstrate the existence of a critical molecular weight for the melt polymer, below which the Stokes-Einstein relation accurately describes the rotational diffusivity of the polymer-grafted nanoparticles and above which the Stokes-Einstein relation ceases to apply. This critical molecular weight was found to correspond to a chain contour length that approximates the hydrodynamic diameter of the nanoparticles.

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.

It is shown that the rotational diffusivity of nanoparticles in polymer solutions spanning the dilute to semi-dilute regimes deviates from the predictions of the Stokes-Einstein (SE) relationship, and that this deviation can be explained by the existence of a polymer depletion layer with the viscosity of the bath solvent. The measurements of the rotational diffusion coefficient of poly(ethylene glycol) (PEG) grafted magnetic nanoparticles in PEG solutions spanning the dilute to semi-dilute regimes and a wide range of polymer molecular weights were obtained from the dynamic magnetic response of the nanoparticles to alternating magnetic fields. Experimental rotational diffusion coefficient values were compared with those predicted by the SE relation using the macroscopic viscosity of the polymer solutions and the hydrodynamic radius of the nanoparticles. Deviations between experimental and SE rotational diffusivity values were observed for nanoparticles in polymer solutions where the radius of gyration of the polymer exceeded the hydrodynamic radius of the particles. A simple model for the rotational hydrodynamic drag on a particle surrounded by a polymer depletion layer was found to describe the experimental rotational diffusivities well, suggesting that the observed phenomenon arises due to the formation of a polymer depletion layer around the nanoparticles.

Nanoparticles are under investigation as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components. Here, we show that rotational and translational diffusion of polymer-coated nanoparticles in quiescent synovial fluid and in hyaluronic acid solutions is well described by the Stokes-Einstein relationship, albeit with an effective medium viscosity that is much smaller than the macroscopic low shear viscosity of the fluid. This effective medium viscosity is well described by an equation for the viscosity of dilute polymer chains, where the additional viscous dissipation arises because of the presence of the polymer segments. These results shed light on the diffusive behavior of polymer-coated inorganic nanoparticles in complex and crowded biological environments, such as in the joint.