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Figure 8.8
Fluorescent microscopy of monolayers of HeLa (top) and KB (bottom)
cells. Cells were incubated with the indicated virus particles (37°C, 2 h), followed
by permeabilization and treatment with anti-CPMV antibody and then with a
green fluorescent secondary antibody conjugate. Nuclei are stained with DAPI
(blue). Scale bar, 10 µm. Reproduced from Destito, G., Yeh, R., Rae, C. S., Finn, M. G.,
and Manchester, M. (2007) Folic acid-mediated targeting of cowpea mosaic virus
particles to tumor cells,
Chem. Biol.
,
14
(10), 1152-1162.
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). A prominent ligand identified using this approach
is the RGD motif. The RGD sequence is a popular targeting ligand used. RGD
peptides recognize the integrins
et al
., 2002; Hajitou
et al
α
b
α
b
and
, which are overexpressed
v
3
v
5
on tumor endothelium and cancer cells (Li
et al
., 2003; Meyer
et al
., 2006;
Sipkins
., 2003).
The RGD motif has been widely exploited in viral nanotechnology, and
genetically engineered as well as chemically modified VNPs displaying RGD
sequences on the particle surface have been developed and tested: RGD has
been chemically attached to CPMV (Sen Gupta
et al
., 1998; Winter
et al
et al
., 2005), PEG and RGD
were linked to TMV (Bruckman
., 2008), and the RGD sequence has
been genetically engineered into M13 phages and AAV vectors (Hajitou
et al
et
 
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