Inorganic nanoparticles for multimodal molecular imaging.

Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle–based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles. I NORGANIC NANOPARTICLES offer many unique advantages for multimodal imaging owing to their unique size- and shape-dependent physical and chemical properties. Inorganic nanoparticles such as magnetic iron oxide nanoparticles (IONPs) are studied as magnetic resonance imaging (MRI) contrast agents, 1 semiconducting quantum dots (QDs) serve as optical probes for intracellular organelles and biomolecules, 2 metallic gold nanoparticles (AuNPs) exhibit unique light scattering patterns for surface-enhanced Raman spectroscopy, 3 and other particles exhibit unique properties useful for molecular imaging. The development of inorganic nanoparticles has grown tremendously owing to advances in synthesis methods and combination with other organic substances. 4 For the last 5 years, the number of publications for ‘‘inorganic nanoparticles’’ on the ISI Web of Knowledge database has increased steadily, totaling a 150% increase. This steady increase is mainly due to the discovery that these nanomaterials offer a unique high aspect ratio platform for multifunctionality, where multiple ligands such as targeting agents, drugs, and radioisotopes can be attached onto one particle for the possibility of molecular targeting, therapeutic delivery, and multimodal imaging. 5 Nanoparticles attached with targeting ligands can enter the cell and pursue specific biomolecules, giving it true molecular imaging capabilities. 6,7 As opposed to adjusting properties in bulk materials, nanoparticle shape and size are easily fine-tuned by the advances in lithography 8,9 and wet-chemistry 10,11 techniques offering tunable magnetic and optical properties for molecular imaging. The different components of the multifunctional nanomaterials can be synthesized in a heterogeneous manner, collectively encapsulated within a nanomaterial, or added onto a singular nanoplatform. Certain nanoparticle synthesis techniques require surface encasing materials to stabilize the nanoparticles and allow for dispersion. 12 The surface coatings can be modified with additional functional groups and multiple imaging agents for multimodal molecular imaging capabilities.