Transferrin-coated gadolinium-labeled human serum albumin nanoparticles

It is necessary to use small molecule contrast agents (CAs) to generate a good contrast in images produced with magnetic resonance imaging (MRI) for the proper diagnosis and monitoring of diseases. Small molecule CAs improve the contrast of only the intravascular tissues, do not cross biological barriers such as the blood–brain barrier (BBB), and are rapidly cleared from circulation through the kidneys (1). Therefore, these CAs cannot be used with MRI for the noninvasive imaging of the brain. As a result, there is an urgent need to develop CAs that can easily cross the BBB and facilitate the early detection of pathological conditions in the brain, such as glioma tumors (2) and Alzheimer’s disease (3), when these diseases are treatable. It is known that CAs that are based on a nanoparticle (NP) scaffold do not diffuse across the blood vessels and have a prolonged circulation half-life. Hence a lower concentration of the NPs, compared with the small molecule CAs, can be used for imaging the vasculature in animals. When NPs are coupled with a CA and a cell-surface binding ligand such as an apolipoprotein or an anti-transferrin receptor antibody, the NP-CA-ligand complex is able to cross cellular barriers, including the BBB, through the process of transcytosis (4). Investigators have shown that NPs made with human serum albumin (HSA; HSA-NPs) are non-toxic, biodegradable, and can be coupled with ligands such as transferrin (HSA-Tf-NP) to produce a complex that can cross the BBB (5). For a brief description of the nature and biological properties of transferrin, see Kolhatkar et al. (6). The use of transferrin for the targeted delivery of drugs in the brain is described by Dufes et al. (7). In another study, HSA-NPs loaded with gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA; Gd-HSA-NPs) and coated with folic acid were shown to be able to cross the BBB and may be used with MRI for the noninvasive imaging of the brain in mice (8). In a continuing effort to develop NP-based CAs that can cross the BBB, Korkusuz et al. coupled the Gd-HSA-NPs with transferrin (Gd-HSA-Tf-NP) and studied the biodistribution of these NPs in normal mice (4). Gd-HSA-Tf-NP was also evaluated for use as a CA with MRI for imaging of the mouse brain.