VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 221

. tArgetIng VnPs to SIteS oF dISeASe

Targeting imaging modalities and therapeutic molecules specifically to sites
of disease while avoiding healthy tissues is an important goal in biomedicine.
Destination-specific delivery of imaging or therapeutic molecules will
facilitate greater specificity and organ avoidance and therefore limit
undesired side effects. The development of phage display technologies has
led to the identification of tumor-specific markers and their ligands, as well
as vascular homing peptides (Arap ., 2006a; Nanda

& St. Croix, 2004; Ruoslahti, 2002). These ligands specifically recognize
receptors overexpressed on diseased tissues. The discovery of these ligands
has revolutionized the field and opened the door for creating specifically
targeted devices (Section 8.4.2).

et al ., 2002; Hajitou et al

8.4.1 Natural VNP-Cell Interacions

8.4.1.1 CPMV—A VNP with Natural Affinity for Mammalian
endothelial Cells

Intravital imaging studies using fluorescent-labeled CPMV particles
indicated that CPMV particles were specifically internalized by endothelial
cells ., 2006). This interaction has been dissected in

detail; it was shown that this interaction is biospecific and mediated by
the mammalian protein vimentin (Koudelka

in vivo (Lewis et al

., 2007, 2009). Vimentin
is a type III intermediate filament predominantly expressed in the cytosol
of cells of mesenchymal origin. Cytosolic vimentin plays a key role in
intracellular dynamics and archtitecture (reviewed in Evans, 1998; Wang &
Stamenovic, 2002). Besides its cytosolic localization, vimentin has recently
been identified as a surface-exposed and/or secreted protein in activated
macrophages (Mor-Vaknin

et al

et al ., 2003), T-lymphocytes (Huet et al ., 2006;

Nieminen et al ., 2006), endothelial cells, specifically in tumor tissue (van

Beijnum .,

2004), among others. Vimentin plays a role in situations such as tumor
development and progression (reviewed in Brabletz

et al ., 2006), and endothelial venules of lymph nodes (Xu et al

et al ., 2005; Gilles et al .,

2003; Kokkinos ., 2007).

The fact that the plant pathogen specifically interacts with a mammalian
protein may be explained by the structural similarities that CPMV shares
with other members of the picornavirus superfamily.

et al

Theiler's murine

encephalomyolitis virus (TMEV), also a member of the picornavirus

superfamily, shows similarities in genetic organization and structure
to CPMV. TMEV has also been shown to directly interact with vimentin
(Nedellec et al ., 1998).