Biomedical Engineering Reference
In-Depth Information
RNAi
RNA interference
scFv
single-chain Fv antibody
SELEX
systematic evolution of ligands by exponential enrichment
siRNA
small interfering RNA
SR-BI
scavenger receptor BI
sTRAIL
tumor necrosis factor-related apoptosis-inducing ligand
SWNT
single-wall carbon nanotube
TAT
trans-activating transcriptional activator
3TC
lamuivudine
Tf
transferrin
TfR
transferrin receptor
TN-C
tenasin-C
TNPO3
Transportin-3
1
Introduction
Since the “magic bullet” dream was first postulated by Dr. Paul Ehrlich in 1906
(Strebhardt and Ullrich
2008
), “targeted therapy” has become a long-standing goal
for human disease treatment but still remains a major challenge for clinical appli-
cations (Zhukov and Tjulandin
2008
; Markman
2008
; Katzel et al.
2009
). Most
therapeutic agents currently in use, such as conventional chemotherapy (Joensuu
2008
), radiotherapy (Harrison et al.
2002
), immunotherapy (Shapira et al.
2010
) or
gene therapy (Whitehead et al.
2009
), generally are not functionalized to selectively
target the site of disease. When these therapeutics agents are systemically adminis-
trated, they nonspecifically distribute throughout the body, thereby significantly
reducing the therapeutic efficacy and leading to harmful side-effects associated
with distribution to non-targeted sites (Langer
1998
).
With the intent and enthusiasm for developing targeted therapeutic drug delivery
strategies, many efforts have been made to develop targeted drug delivery strategies
capable of selectively transporting drug to a specific site of disease (Yu et al.
2010
;
Zhou and Rossi
2009
; Kim et al.
2009c
; Levy-Nissenbaum et al.
2008
; Allen
2002
).
The strategy mainly relies on specific interaction between the targeting ligand and
its receptors expressed on the diseased cells or tissues. Such ligand-directed recog-
nization events consequently increase the local concentration of the drug in the
targeted cells or tissues. Furthermore, after the ligand-receptor binding, the cellular
receptors are readily internalized and rapidly re-expressed on the cell surface to
allow repeated targeting and internalization. Depending on the types of therapeutic
agents or drug formulation, it is worth noting that internalization may be dispensable
in some therapies (Allen
2002
). For example, for antibody-directed enzyme-prodrug
anticancer therapy (Senter and Springer
2001
), the enzyme-prodrug is first selec-
tively accumulated on the cell surface
via
antibody-receptor interaction; subsequently,
it is activated into an anticancer drug by the enzyme that only functionalizes at the
cell surface. Additionally, in the radioimmunotherapy (Ercan and Caglar
2000
;
Goldenberg
2002
), antibody-conjugated beta- or alpha- radionuclides can directly
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