Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.

Since the use of magnetic nanocrystals as probes for biomedical system is attractive, it is important to develop optimal synthetic protocols for high-quality magnetic nanocrystals and to have the systematic understanding of their nanoscale properties. Here we present the development of a synthetically controlled magnetic nanocrystal model system that correlates the nanoscale tunabilities in terms of size, magnetism, and induced nuclear spin relaxation processes. This system further led to the development of high-performance nanocrystal-antibody probe systems for the diagnosis of breast cancer cells via magnetic resonance imaging.

The conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications such as drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this Letter, we demonstrate a significant increase in the efficiency of magnetic thermal induction by nanoparticles. We take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power, which is a gauge of the conversion efficiency. The optimized core-shell magnetic nanoparticles have specific loss power values that are an order of magnitude larger than conventional iron-oxide nanoparticles. We also perform an antitumour study in mice, and find that the therapeutic efficacy of these nanoparticles is superior to that of a common anticancer drug.

Synthetic magnetic nanoparticles (MNPs) are emerging as versatile probes in biomedical applications, especially in the area of magnetic resonance imaging (MRI). Their size, which is comparable to biological functional units, and their unique magnetic properties allow their utilization as molecular imaging probes. Herein, we present an overview of recent breakthroughs in the development of new synthetic MNP probes with which the sensitive and target-specific observation of biological events at the molecular and cellular levels is possible.

Current biomedical imaging techniques including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed X-ray tomography (CT) are vital in the diagnosis of various diseases. Each imaging modality has its own merits and disadvantages, and a single technique does not possess all the required capabilities for comprehensive imaging. Therefore, multimodal imaging methods are quickly becoming important tools for state-of-the-art biomedical research and clinical diagnostics and therapeutics. In this Account, we will discuss synergistically integrated nanoparticle probes, which will be an essential tool in multimodal imaging technology. When inorganic nanoparticles are introduced into biological systems, their extremely small size and their exceptional physical and chemical properties make them useful probes for biological diagnostics. Nanoparticle probes can endow imaging techniques with enhanced signal sensitivity, better spatial resolution, and the ability to relay information about biological systems at the molecular and cellular levels. Simple magnetic nanoparticles function as MRI contrast enhancement probes. These magnetic nanoparticles can then serve as a core platform for the addition of other functional moieties including fluorescence tags, radionuclides, and other biomolecules for multimodal imaging, gene delivery, and cellular trafficking. For example, MRI-optical dual-modal probes composed of a fluorescent dye-doped silica (DySiO(2)) core surrounded by magnetic nanoparticles can macroscopically detect neuroblastoma cancer cells via MRI along with subcellular information via fluorescence imaging. Magnetic nanoparticles can also be coupled to radionuclides ((124)I) to construct MRI-PET dual-modal probes. Such probes can accurately detect lymph nodes (LNs), which are critical for assessing cancer metastasis. In vivo MRI/PET images can clearly identify small (approximately 3 mm) LNs along with precise anatomical information. Systems using multicomponent nanoparticles modified with biomolecules can also monitor gene expression and other markers in cell therapeutics studies. We have used hybrid stem cell-magnetic nanoparticle probes with MRI to monitor in vivo stem cell trafficking. MRI with hybrid probes of magnetic nanoparticles and adenovirus can detect target cells and can monitor gene delivery and the expression of green fluorescent proteins optically. Each component of such multimodal probes complements the other modalities, and their synergistic materials properties ultimately provide more accurate information in in vitro and in vivo biological systems.

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.

The unique properties of magnetic nanocrystals provide them with high potential as key probes and vectors in the next generation of biomedical applications. Although superparamagnetic iron oxide nanocrystals have been extensively studied as excellent magnetic resonance imaging (MRI) probes for various cell trafficking, gene expression, and cancer diagnosis, further development of in vivo MRI applications has been very limited. Here, we describe in vivo diagnosis of cancer, utilizing a well-defined magnetic nanocrystal probe system with multiple capabilities, such as small size, strong magnetism, high biocompatibility, and the possession of active functionality for desired receptors. Our magnetic nanocrystals are conjugated to a cancer-targeting antibody, Herceptin, and subsequent utilization of these conjugates as MRI probes has been successfully demonstrated for the monitoring of in vivo selective targeting events of human cancer cells implanted in live mice. Further conjugation of these nanocrystal probes with fluorescent dye-labeled antibodies enables both in vitro and ex vivo optical detection of cancer as well as in vivo MRI, which are potentially applicable for an advanced multimodal detection system. Our study finds that high performance in vivo MR diagnosis of cancer is achievable by utilizing improved and multifunctional material properties of iron oxide nanocrystal probes.

Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated the ability to contain and release cargos with mediation by gatekeepers. Magnetic nanocrystals have the ability to exhibit hyperthermic effects when placed in an oscillating magnetic field. In a system combining these two materials and a thermally sensitive gatekeeper, a unique drug delivery system can be produced. A novel material that incorporates zinc-doped iron oxide nanocrystals within a mesoporous silica framework that has been surface-modified with pseudorotaxanes is described. Upon application of an AC magnetic field, the nanocrystals generate local internal heating, causing the molecular machines to disassemble and allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231) were treated with doxorubicin-loaded particles and exposed to an AC field, cell death occurred. This material promises to be a noninvasive, externally controlled drug delivery system with cancer-killing properties.