Biology Reference
In-Depth Information
novel functionalities. These interactions have also been widely used for
immobilization of VNPs on solid supports and the fabrication of multilayered
arrays, which will be discussed in Chapter 7.
Biotinylated CCMV particles were joined with biotinylated antibodies
using streptavidin as a linker (Fig. 4.16). Antibody-interlinked CCMV particles
were then utilized for targeting biofilm-forming bacteria. These principles
were extended, and dual-functionalized targeted, therapeutic CCMV particles
were designed. Ruthenium complexes were attached to antibody-interlinked
CCMV particles; the ruthenium complexes served as photosensitizers for
photodynamic cell killing (Suci
, 2007a,b) (see also Chapter 8).
A range of non-covalent strategies has been developed to specifically link
targeting molecules to the surface of Ad vectors to achieve tissue-specific
targeting of the gene delivery vectors (reviewed in Barnett
et al.
, 2002;
Campos & Barry, 2007; Mizuguchi & Hayakawa, 2004; Singh & Kostarelos,
2009). This includes the use of fusion proteins that combine a capsid-binding
domain and a cell-binding ligand. Antibodies or antibody fragments specific
for the Ad coat proteins or soluble coxsackievirus and adenovirus receptor
(CAR) domain (which is exposed on the Ad particle surface) are typically
used as capsid-binding domains. Cell- and tissue-specific ligands can be
peptides, proteins, antibodies, or antibody fragments. Some examples include
epidermal growth factor (EGF), fibroblast growth factor (FGF-2), gastrin-
releasing peptides (GRPs), and antibodies targeted to carcinoembryonic
antigen (CEA). Similar strategies have been explored for the gene delivery
vehicle AAV (reviewed in Baker, 2003; Kwon & Schaffer, 2008).
et al.
Figure 4.16
Cartoon showing the strategy used to target CCMV to
Staphylococcus
aureus
(bacterium); streptavidin (StAv) was used to couple biotinylated anti-SpA
antibody (Ab) to CCMV, which was dual labeled with biotin (B) and an imaging
agent (IA). Reproduced with permission from Suci, P. A., Berglund, D. L., Liepold, L.,
Brumfield, S., Pitts, B., Davison, W., Oltrogge, L., Hoyt, K. O., Codd, S., Stewart, P. S.,
Young, and M., Douglas, T. (2007) High-density targeting of a viral multifunctional
nanoplatform to a pathogenic, biofilm-forming bacterium,
Chem. Biol.
,
14
(4),
387-398.
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