title: Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies.
abstract: Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, approximately 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM-1 s-1 (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM-1 s-1 (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: Ankona
authors.initials: A
authors.lastname: Datta
authors.forename: Mauro
authors.initials: M
authors.lastname: Botta
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Francis
mesh_terms: D002213:Capsid / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005682:Gadolinium / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods; D017909:Levivirus / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010316:Particle Size; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D005682:Gadolinium