Superparamagnetic nanoparticles for enhanced magnetic resonance and multimodal imaging

Magnetic resonance imaging (MRI) is a powerful tool for noninvasive tomographic imaging of biological systems with high spatial and temporal resolution. Superparamagnetic (SPM) nanoparticles have emerged as highly effective MR contrast agents due to their biocompatibility, ease of surface modification and magnetic properties. Conventional nanoparticle contrast agents suffer from difficult synthetic reproducibility, polydisperse sizes and weak magnetism. Numerous synthetic techniques and nanoparticle formulations have been developed to overcome these barriers. However, there are still major limitations in the development of new nanoparticle-based probes for MR and multimodal imaging including low signal amplification and absence of biochemical reporters. To address these issues, a set of multimodal (T2/optical) and dual contrast (T1/T2) nanoparticle probes has been developed. Their unique magnetic properties and imaging capabilities were thoroughly explored. An enzyme-activatable contrast agent is currently being developed as an innovative means for early in vivo detection of cancer at the cellular level.;Multimodal probes function by combining the strengths of multiple imaging techniques into a single agent. Co-registration of data obtained by multiple imaging modalities validates the data, enhancing its quality and reliability. A series of T2/optical probes were successfully synthesized by attachment of a fluorescent dye to the surface of different types of nanoparticles. The multimodal nanoparticles generated sufficient MR and fluorescence signal to image transplanted islets in vivo.;Dual contrast T1/T2 imaging probes were designed to overcome disadvantages inherent in the individual T1 and T2 components. A class of T1/T2 agents was developed consisting of a gadolinium (III) complex (DTPA chelate or DO3A macrocycle) conjugated to a biocompatible silica-coated metal oxide nanoparticle through a disulfide linker. The disulfide linker has the ability to be reduced in vivo by glutathione, releasing large payloads of signal-enhancing T1 probes into the surrounding environment. Optimization of the agent occurred over three sequential generations, with each generation addressing a new challenge. The result was a T2 nanoparticle containing high levels of conjugated T1 complex demonstrating enhanced MR relaxation properties.;The probes created here have the potential to play a key role in the advancement of nanoparticle-based agents in biomedical MRI applications.