The use of magnetism in medicine has changed dramatically since its first application by the ancient Greeks in 624 BC. Now, by leveraging magnetic nanoparticles, investigators have developed a range of modern applications that use external magnetic fields to manipulate biological systems. Drug delivery systems that incorporate these particles can target therapeutics to specific tissues without the need for biological or chemical cues. Once precisely located within an organism, magnetic nanoparticles can be heated by oscillating magnetic fields, which results in localized inductive heating that can be used for thermal ablation or more subtle cellular manipulation. Biological imaging can also be improved using magnetic nanoparticles as contrast agents; several types of iron oxide nanoparticles are US Food and Drug Administration (FDA)-approved for use in magnetic resonance imaging (MRI) as contrast agents that can improve image resolution and information content. New imaging modalities, such as magnetic particle imaging (MPI), directly detect magnetic nanoparticles within organisms, allowing for background-free imaging of magnetic particle transport and collection. “Lab-on-a-chip” technology benefits from the increased control that magnetic nanoparticles provide over separation, leading to improved cellular separation. Magnetic separation is also becoming important in next-generation immunoassays, in which particles are used to both increase sensitivity and enable multiple analyte detection. More recently, the ability to manipulate material motion with external fields has been applied in magnetically actuated soft robotics that are designed for biomedical interventions. In this review article, the origins of these various areas are introduced, followed by a discussion of current clinical applications, as well as emerging trends in the study and application of these materials.

Millions of people a year receive magnetic resonance imaging (MRI) contrast agents for the diagnosis of conditions as diverse as fatty liver disease and cancer. Gadolinium chelates, which provide preferred T1 contrast, are the current standard but face an uncertain future due to increasing concerns about their nephrogenic toxicity as well as poor performance in high‐field MRI scanners. Gadolinium‐containing nanocrystals are interesting alternatives as they bypass the kidneys and can offer the possibility of both intracellular accumulation and active targeting. Nanocrystal contrast performance is notably limited, however, as their organic coatings block water from close interactions with surface Gadoliniums. Here, these steric barriers to water exchange are minimized through shape engineering of plate‐like nanocrystals that possess accessible Gadoliniums at their edges. Sulfonated surface polymers promote second‐sphere relaxation processes that contribute remarkable contrast even at the highest fields (r1 = 32.6 × 10−3 m Gd−1 s−1 at 9.4 T). These noncytotoxic materials release no detectable free Gadolinium even under mild acidic conditions. They preferentially accumulate in the liver of mice with a circulation half‐life 50% longer than commercial agents. These features allow these T1 MRI contrast agents to be applied for the first time to the ex vivo detection of nonalcoholic fatty liver disease in mice.

Iron oxide nanoparticles are an FDA-approved and gadolinium-free alternative to conventional magnetic resonance imaging (MRI) contrast agents. While their magnetic cores are responsible for T 2 contrast, the nonmagnetic polymers at the particle interfaces can affect the diffusion of bulk water near the particles. We show here how this interaction can alter the relaxation dynamics of water protons and, consequently, the nanoparticle's contrast performance. Libraries of iron oxide nanocrystals of different core diameters and surface coatings can form biocompatible, non-cytotoxic, and colloidally stable suspensions with excellent MRI properties. Both the grafting density and thickness of polymer coatings influence the amount of time water protons spend around a nanoparticle and thus their contrast agent performance. Characterization of the diameter-dependent contrast performance of these materials revealed that nanoparticles with dense, hydrophilic polymer coatings reached the static dephasing regime, and optimal T 2 relaxivity, at smaller dimensions than other systems. We rationalized that such coatings offered a slow compartment for water diffusion near the magnetic particle, resulting in an effective diffusion constant lower than bulk water. By manipulating the surface coating and core diameter together, we could generate a material with one of the largest T 2 relaxivities ever reported (510 mM −1 s −1 ) for an isolated nanocrystal. This conceptual framework can explain the complex structure−performance trends of this class of T 2 contrast agents and those already reported in the existing literature. Water diffusion at iron oxide nanocrystals (IONCs) interfaces is an essential consideration in designing sensitive and possibly responsive T 2 MRI contrast agents.