VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 223

The natural interactions of CPMV with the mammalian system were
further exploited, and targeting to sites of inflammation in the central
nervous system (CNS) was demonstrated (Shriver ., 2009). In brief,

mice infected with neurotropic mouse hepatitis virus were studied; this is a
commonly used animal model for the human demyelinating disease multiple
sclerosis. CPMV was found to localize mainly to the CNS endothelium that
contained an intact blood-brain barrier. In inflammatory lesions containing
macrophage/microglial cell infiltration and IgG, which indicates breakdown
of the blood-brain barrier, CPMV was also detected in the brain parenchyma
(Shriver

et al

., 2009). This may open the door for targeted treatment of
inflammatory disease of CNS.

et al

8.4.1.2 Designing VNPs for Targeing Applicaions

Some cells and tissues in diseased sites express a different set of receptors
on their cell surface compared to cells in healthy tissues. Cells in tumor
tissue are rapidly proliferating. Therefore, tumor cells overexpress certain
proteins and receptors on the cell surface that are involved in signaling
nutrient uptake, cell growth and division. As selectively and significantly
overexpressed, these receptors provide a target for tissue-specific delivery
of imaging modalities or therapeutics.
The receptor for the protein transferrin (Tf ), for example, is
overexpressed on several tumor cells. Tf is a circulating iron storage protein.
Tf binds to the Tf receptors (TfR) and is internalized. Inside the cells, iron
is released and Tf recycled. Iron is in high demand during cell growth and
cell proliferation; hence, proliferating tumor cells overexpress TfR on their
cell surface. Normal, non-dividing cells express few to negligible numbers of
TfR on their cell surface. In stark contrast, tumor cells express 10 or more

TfR per cell. Targeting TfR is thus expected to be a promising strategy to
specifically target cancer (Becker

5

et al ., 2000; Bridges & Smith, 1985; Du et

al ., 2002; Gomme et al ., 2005; Inoue et al ., 1993; Li & Qian, 2002; Li et al .,

2002; Qian ., 2000).

Delivering VNPs to tumor cells exploiting TfR has been studied using
MS2, CPMV, and CPV (Brown

et al ., 2002; Ryschich et al ., 2004; Sato et al

.,
2006a). For MS2 and CPMV, the protein Tf has been covalently attached and
displayed on the particle surface (Brown

et al ., 2002; Sen Gupta et al ., 2005; Singh et al

., 2005);
this was achieved using the principles discussed in Chapter 4. Tf-targeted
MS2 particles were further modified with therapeutic molecules and
targeted drug delivery was demonstrated (Brown

et al ., 2002; Sen Gupta et al

., 2002) (see Section
8.5). TfR targeting can be achieved making use of the natural receptor-

et al