P22 viral capsids as nanocomposite high-relaxivity MRI contrast agents

Mol Pharm. 2013 Jan 7;10(1):11-7. doi: 10.1021/mp300208g. Epub 2012 Jul 16.

Abstract

Attachment of multiple chelated Gd(3+) ions to the interior of bacteriophage P22 viral capsids affords nanoscale MRI contrast agents with extremely high relaxivity values. Highly fenestrated "wiffleball" morphology is unique to P22 and assures water exchange between the environment and interior cavity of the capsid. The cavity of P22 "wiffleball" was functionalized with a branched oligomer comprising multiple DTPA-Gd complexes resulting in an impressive payload of 1,900 Gd(3+) ions inside each 64 nm capsid. High relaxivities of r(1,ionic) = 21.7 mM(-1) s(-1) and r(1,particle) = 41,300 mM(-1) s(-1) at 298 K, 0.65 T (28 MHz) are reported, with r(1)/r(2) ratio of 0.80 and optimized rotational correlation time for this system. Specific design modifications are suggested for future improvements of viral capsid-based MRI contrast agents directed toward clinical translation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteriophage P22 / chemistry*
  • Capsid / chemistry*
  • Contrast Media / chemistry*
  • Gadolinium / chemistry
  • Gadolinium DTPA / chemistry
  • Magnetic Resonance Imaging / methods*
  • Nanocomposites / chemistry*

Substances

  • Contrast Media
  • Gadolinium
  • Gadolinium DTPA