| Magnetic nanoparticles (MNPs) have attracted enormous research attention due to their unique magnetic properties that enable the detection by the non-invasive medical imaging modality---magnetic resonance imaging (MRI). By incorporating advanced features, such as specific targeting, multimodality, therapeutic delivery, the detectability and applicability of MNPs have been dramatically expanded. Smart and rational design on structure, composition and surface chemistry is essential to achieving desired properties in MNP systems, such as high sensitivity and colloidal stability, target specificity and/or multimodality. The goal of this research is to develop MNP-based platforms for the detection, diagnosis and treatment of cancer. MNPs with high contrast enhancement were coated with poly(ethylene glycol) (PEG)-based polymers to render aqueous stability and confer therapeutic-loading capability. Tumor-specific MNPs were developed by functionalization of nanoparticles with chlorotoxin (CTX) or arginine-glycine-aspartic acid (RGD) that targets, respectively, MMP-2 receptor or alphavbeta3 integrin overexpressed on a variety of cancer cells. The effects of ligands' molecular targets on the temporal and spatial distribution of MNPs within tumors were also investigated both in vitro and in vivo. All MNPs exhibited excellent long-term stability in cell culture media. CTX-labeled MNP exhibited sustained accumulation, penetration and distribution in the tumor mass. These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. To demonstrate the ability of nanoparticles as drug carrier, anthracyline chemotherapeutic drugs doxorubicin and mitoxantrone were attached to iron oxide nanoparticles. The theragnostic nanoparticles showed sufficient contrast enhancement and comparable anti-neoplastic efficacy in vitro. With flexible surface chemistry, our nanoparticle platform can be used in a modular fashion to conjugate biomolecules for intended applications, and the functionalized nanoparticle systems retain a prolonged stability and exhibit high tumor specificity. The study would establish the foundation for future development of integrated theragnostic systems for the treatment of cancer and other complex diseases. |
