Decades of research focused on size and shape control of iron oxide nanoparticles have led to methods of synthesis that afford excellent control over physical size and shape, but comparatively poor control over magnetic properties. Popular synthesis methods based on thermal decomposition of organometallic precursors in the absence of oxygen have yielded particles with mixed iron oxide phases, crystal defects and poorer than expected magnetic properties, including the existence of a thick “magnetically dead layer” experimentally evidenced by a magnetic diameter significantly smaller than the physical diameter. Here, we show how single crystalline iron oxide nanoparticles with few defects and similar physical and magetic diameter distributions can be obtained by introducing molecular oxygen as one of the reactive species in the thermal decomposition synthesis. This is achieved without the need for any post-synthesis oxidation or thermal annealing. These results address a significant challenge in the synthesis of nanoparticles with predictable magnetic properties and pave way to advances in applications of magnetic nanoparticles.

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.

Nanoscaled drug carriers have been developed to accumulate in tumors and release a drug cargo either passively or in response to a local stimulus. However, strategies that rely on passive release or response to a local stimulus do not allow for spatial and temporal control of drug delivery. These limitations motivate interest in drug delivery platforms that release cargo in response to an external stimulus. This contribution describes magnetically controlled nanocarriers (MCNCs) that release heat and a drug cargo in response to an applied alternating magnetic field (AMF). The MCNCs consist of a hydrophobic core of superparamagnetic iron oxide nanoparticles that release heat in response to an AMF and a thermoresponsive polymer that releases a molecular cargo via breakage of thermally labile Diels−Alder (DA) bonds. The nanocarriers are coated with polyethylene glycol-block-polylactic acid (PEG 4.9kD -PLA 6.0kD ) block copolymer to confer colloidal stability and water solubility. The MCNCs are assembled through flash nanoprecipitation, a rapid approach to making nanoparticles that is scalable and provides control of size and composition. Release experiments show that application of an AMF results in on-demand heat and drug release. The AMF-actuated release ceases when the field is turned off, and multiple applications of AMF result in programmable release. The amount of release is tunable via the AMF field strength and can be spatially controlled using selection magnetic field gradients. These results suggest that a potent combination of magnetic hyperthermia and drug release can be actuated in a desired region.

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.

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