Biomedical Engineering Reference
In-Depth Information
et al. reported tumor extracellular pH-triggered TAT-presenting micelles. The
TAT moieties were anchored to a PEG micelle corona and shielded at pH .7.0
by their electrostatic complexation with poly(methacryloyl sulfadimethoxine)
(anionic PSD)-PEG (PSD-b-PEG) diblock copolymer. At pH 6.6, however, PSD
turned to a nonionized form and fell off the TAT, exposing it and enabling the
micelle a fast cellular uptake.
186
Another design was to anchor TAT onto the PEG
corona through a pH-sensitive PHis spacer. At pH 7.4, the PHis was water
insoluble, which kept the TAT moieties buried in the PEG corona. At pH lower
than 7.2, however, ionization of the PHis spacer made it water soluble, which
stretched it, exposing the TAT on the corona surface.
187
The most common approach enabling a carrier to become sticky to the cell
membrane is to decorate it with a ligand whose receptors are overexpressed on the
cancer-cell membrane. The ligand-receptor binding enables receptor-mediated
endocytosis, promoting cellular uptake.
11,188
Only a few ligands are needed for
rapid internalization.
189
More ligand groups can theoretically increase uptake, but
a high surface ligand density may make the carrier less stealthy as a result of
opsonization-mediated clearance.
190
Many examples of targeting ligands include
folic acid,
191
peptides,
192-194
antibodies,
195-197
transferrin,
198
aptamers,
199,200
and
other moieties
201
that have been tested and subsequently reviewed.
2,202
d
n
4
y
3
n
g
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2
Figure
3.11
(A) The charge-reversal concept for drug delivery. Reprinted with
permission from ref. 14. Copyright 2010 Elsevier; (B) The pH-responsive
three-layered nanoparticles (3LNPs). Reprinted with permission from
ref. 16. Copyright 2008 American Institute of Chemical Engineers.
