VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 224

binding properties of CPV, which utilizes TfR in order to infect cells. Non-
infectious and non-replicating CPV VLPs were developed that preserve
binding to TfR (Singh et al ., 2006a). Delivery of dye-labeled CPV VLPs to

different cancer cell lines in vitro has been demonstrated (Fig. 8.7) (Singh et

al ., 2006a).

Figure 8.7 (CPV) VLPs into HeLa

cells (human cervical cancer cell line). HeLa cells incubated with Texas red-labeled
transferrin (red) and CPV VLPs were washed and fixed. Labeled antibodies (green)
were used to detect the presence of CPV VLPs in the cells by fluorescence confocal
microscopy. (a) CPV VLPs are seen as green areas in the cytoplasm, (b) localization
of Texas red-transferrin (red) and (c) merged picture showing co-localization of CPV-
VLPs and transferrin in yellow. Scale bar, 25 µm. Reproduced from Singh, P., Destito,
G., Schneemann, A., and Manchester, M. (2006) Canine parvovirus-like particles, a
novel nanomaterial for tumor targeting,

Binding and internalization of Canine parvovirus

J. Nanobiotechnol. , 4, 2.

Another receptor that is overexpressed specifically on tumor cells is
the receptor for folic acid (FA). FA is a vitamin required during growth
and development. Proliferating cells require high levels of this vitamin and
therefore overexpress the FA receptor (FR). Targeting nanomaterials to FR
has been shown to be a promising strategy (Cafolla et al ., 2002; Chen et al .,

1998; Leamon & Low, 1992, 1993, 2002a,b; Reddy & Low, 1998; Turek et al .,

1993; Wang & Low, 1998). The VNPs CPMV and Hibiscus chlorotic ringspot

virus (HCRSV) have been covalently modified with FA. Multivalent display

of FA on the particle surface facilitated cell internalization by tumor cells
overexpressing FR (Destito

., 2007). In the case of CPMV,
particles were covalently modified with PEG and FA; PEG provides shielding
of the natural CPMV interactions, and FA facilitated target specificity (Fig.
8.8) (Destito

et al ., 2007; Ren et al

., 2007). The FR-targeting strategy has been further
developed for targeted delivery of the chemotherapeutic doxorubicin using
the HCRSV platform (see Section 8.5) (Ren

et al

et al ., 2007).