Localization of gadolinium-loaded CPMV to sites of inflammation during central nervous system autoimmunity

Abstract

Contrast-enhanced magnetic resonance imaging (MRI) allows rapid non-invasive diagnosis of central nervous system (CNS) pathologies such as multiple sclerosis (MS). Current gadolinium-based contrast agents must be administered at high doses, are excreted by the kidney, and some formulations are associated with toxicity in patients with renal insufficiency. The development of nanoparticle carriers for targeted delivery of gadolinium to sites of disease would increase specificity, as well as decrease the dose of gadolinium required to obtain sufficient contrast for disease diagnosis. The plant virus, cowpea mosaic virus (CPMV), is a biocompatible nanoparticle platform for imaging applications. Gadolinium is rapidly incorporated into the interior of the CPMV capsid without disrupting particle integrity, and CPMV–Gd particles have relaxivity comparable to gadolinium chelates used clinically. Here we examine the ability of gadolinium-loaded CPMV particles (CPMV–Gd) to localize to lesions in the CNS in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). The in vivo distribution of gadolinium-loaded CPMV (CPMV–Gd) was examined within the periphery and central nervous system (CNS). CPMV accumulated in inflammatory lesions within the brain and spinal cord, and specifically associated with CD11b⁺ and CD11c⁺ cells. These results demonstrate that CPMV is an attractive nanoparticle chelate for gadolinium for in vivo applications and may have clinical utility as a contrast agent for the detection of autoimmune demyelinating diseases of the CNS.