Early detection and treatment of disease is the most important component of a favorable prognosis. Biomedical researchers have thus invested tremendous effort in improving imaging techniques and treatment methods. Over the past decade, concepts and tools derived from nanotechnology have been applied to overcome the problems of conventional techniques for advanced diagnosis and therapy. In particular, advances in nanoparticle technology have created new paradigms for theranostics, which is defined as the combination of therapeutic and diagnostic agents within a single platform. In this Account, we examine the potential advantages and opportunities afforded by magnetic nanoparticles as platform materials for theranostics. We begin with a brief overview of relevant magnetic parameters, such as saturation magnetization, coercivity, and magnetocrystalline anisotropy. Understanding the interplay of these parameters is critical for optimizing magnetic characteristics needed for effective imaging and therapeutics, which include magnetic resonance imaging (MRI) relaxivity, heat emission, and attractive forces. We then discuss approaches to constructing an MRI nanoparticle contrast agent with high sensitivity. We further introduce a new design concept for a fault-free contrast agent, which is a T1 and T2 dual mode hybrid. Important capabilities of magnetic nanoparticles are the external controllability of magnetic heat generation and magnetic attractive forces for the transportation and movement of biological objects. We show that these functions can be utilized not only for therapeutic hyperthermia of cancer but also for controlled release of cancer drugs through the application of an external magnetic field. Additionally, the use of magnetic nanoparticles to drive mechanical forces is demonstrated to be useful for molecular-level cell signaling and for controlling the ultimate fate of the cell. Finally, we show that targeted imaging and therapy are made possible by attaching a variety of imaging and therapeutic components. These added components include therapeutic genes (small interfering RNA, or siRNA), cancer-specific ligands, and optical reporting dyes. The wide range of accessible features of magnetic nanoparticles underscores their potential as the most promising platform material available for theranostics.

Magnetic nanoparticles have been extensively explored as a versatile platform for magnetic resonance imaging (MRI) contrast agents due to their strong contrast enhancement effects together with the platform capability for multiple imaging modalities. In this tutorial review, we focus on recent progress in the use of magnetic nanoparticles for MRI contrast agents and multi-mode imaging agents such as T1-T2 MRI, MRI-optical, and MRI-radioisotopes. This review also highlights emerging magnetic imaging techniques such as magnetic particle imaging (MPI), magneto-motive ultrasound imaging (MMUS), and magneto-photoacoustic imaging (MPA).

Achieving high accuracy in the imaging of biological targets is a challenging issue. For MRI, to enhance imaging accuracy, two different imaging modes with specific contrast agents are used; one is T1 type for a "positive" MRI signal and the other is T2 type for a "negative" signal. Conventional contrast agents response only in a single imaging mode and frequently encounter ambiguities in the MR images. Here, we propose a "magnetically decoupled" core-shell design concept to develop a dual mode nanoparticle contrast agent (DMCA). This DMCA not only possesses superior MR contrast effects, but also has the unique capability of displaying "AND" logic signals in both the T1 and T2 modes. The latter enables self-confirmation of images and leads to a greater diagnostic accuracy. A variety of novel DMCAs are possible and the use of DMCAs can potentially bring the accuracy of MR imaging of diseases to a higher level.By combining complementary information obtained from various imaging methods, including magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT) and optical microscopy, multi-modal imaging techniques have been devised to increase the accuracy of disease diagnosis. 1 However, even when multimodal techniques are employed, inherent problems still exist. For example, image matching difficulties caused by relocating biological samples and the discrepancies resulting from different depth penetrations and spatial/time resolutions of multiple imaging devices can lead to inaccuracies. 1a,b Therefore, the development of dual imaging strategies that employ a single instrumental system is another important approach.MRI is a powerful technique for tomographic images of biological targets in a non-invasive manner with a high spatial resolution. In MRI, relaxation time of protons of water in the sample is measured. Contrast agents are employed to greatly change proton relaxation rates and to enhance visualization of the differences between normal and disease tissues. T1 contrast agents, comprised typically of paramagnetic materials such as Gd complexes and Mn oxide nanoparticles, facilitate spin-lattice relaxation of protons causing a positive (or bright) MR image. 2,3 On the other hand, T2 contrast agents that commonly consist of superparamagnetic nanoparticles (e.g. iron oxide) cause protons in their vicinity to undergo spin-spin relaxation which gives rise to negative (or dark) MR images. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA dual mode strategy for MRI, where two different T1 and T2 imaging modes are utilized simultaneously, can potentially give highly sensitive and accurate information. For such purposes, ultra small superparamagnetic iron oxide (USPIO), which displays enhanced T1 contrast effects, has been developed, but their T2 contrast effects are weak. 6 Although a system comprised of FeCo nanoparticles is the only one reported thus far that exhibits high T1 and T2 contrast effects, 7 an understanding of the mechanism by which this...

One of the holy grails in biomedical imaging technology is to achieve accurate imaging of biological targets. The development of sophisticated instrumentation and the use of contrast agents have improved the accuracy of biomedical imaging. However, the issue of false imaging remains a problem. Here, we developed a dual-mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has the ability to perform "AND logic gate" algorithm to eliminate false errors (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the artifact filtering capability of AFIA in MRI phantoms and further demonstrate that artifact-free imaging of stem cell migration is possible in vivo.

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