Dendrimer-Functionalized Shell-crosslinked Iron Oxide Nanoparticles for In-Vivo Magnetic Resonance Imaging of Tumors**

Non-invasive diagnosis and detection of early-stage tumors is regarded as one of the current challenges in the biomedical sciences. Magnetic resonance (MR) imaging is a powerful, non-invasive imaging technique because of its high spatial resolution and tomographic capabilities. However, the signal sensitivity of MR imaging for specific biological targets is largely dependent on the specificity and selectivity of the ligand used to target magnetic nanoparticles (NPs) to specific tissues. Development of tumor-targeted magnetic NPs is necessary to enhance the MR signal sensitivity for in-vivo tumor detection. Various proteins such as transferrin, anti-carcinoembryonic antigen monoclonal antibody rch 24, herceptin, and chlorotoxin have been conjugated onto iron oxide NP surfaces. Unfortunately, these protein ligands tend to display immunogenecity and the biological macromolecules used are very expensive and not available for many types of cancer, which thereby limits their applications. One of the most widely used cancer-targeting ligands is folic acid (FA), which targets FA receptors (FAR) that are overexpressed in several human carcinomas including breast, ovary, endometrium, kidney, lung, head and neck, brain, and myeloid cancers. Several groups have investigated the conjugation of folic acid (FA) onto iron oxide NPs for targeting tumor cells. However, many of these reports are limited to in-vitro studies. This is largely a result of difficulties related to the in-vivo stability and