Challenges and Opportunities in Gene Delivery - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 57

overexpressed on the target cells. The ligand-targeted therapeutics are a successful
means of improving the site-specific desired action as well as in reducing the selective
toxicity of the drugs and DNA. This strategy has been very successful in targeting the
complexes to tissues such as the liver and brain [83,84] and has also been effective in
selective targeting of tumor cells. More than 100 ligand-targeted therapeutics are cur-
rently in clinical trials, with a few in the market and more to come [85] .
The choice of targeting ligand is governed by some important considerations such
as density of receptor expression of the targeting ligand, receptor-mediated cellular
internalization, and availability and price of the ligands. Some ligands like folate,
transferrin, and RGD peptides may at times also bind to nontarget tissues because
of receptor availability. Also, for receptors such as folate and transferrin, signifi-
cant levels of these materials may be available in the body (through diet), and these
free ligands will also compete for binding with the ligand-targeted therapeutics. The
monoclonal antibodies show a specific target selectivity and may themselves show
the desired response, as in the case of the cytotoxic effect of herceptin in breast
cancer [86] . These antibodies are expensive and difficult to handle, but the major
problem may arise because of the immunogenicity of some antibodies, which can
be addressed by using the antibody fragments instead of the complete antibodies.
Some of the ligands that have been used in ligand-targeted therapeutics are shown in
Table 2.3 .

Table 2.3 Targeting Ligands Attached to Polyplexes and Lipoplexes Along with
Target Receptors and Cells

No. Targeting Ligand Target Cells/Organ Reference

1 RGD and YGSIR

peptide

Cellular adhesion
molecules such as
3 integrin

Vascular endothelial
cells in solid tumor

[87]

2 NGR peptide Aminopeptidase

N (CD 13)

Vascular endothelial
cells in solid tumor

[88]

3 Folic acid/folate Folate receptor Cancer cells

overexpressing the
folate receptor

[35]

4 Transferrin Transferrin

receptors

Cancer cells
overexpressing the
transferrin receptor

[33]

5 Galactosamine Galactosamine

receptors on
hepatocytes

Hepatoma [89]

6 Anisamide, haloperidol Sigma receptors Breast cancer, lung

cancer

[90,91]

7 Hyaluronic acid CD-44 receptors Lung, ovarian, and

breast cancer

[92]

8 Monoclonal antibodies

such as anti-CD22,
herceptin, and so on

Surface receptors
specific to these
antibodies

Various tumor cells [86]