Biomedical Engineering Reference
In-Depth Information
Fig. 14
Interaction of the multifunctional pH-responsive pharmaceutical nanocarrier with the
target cell. Local stimuli-dependent removal of protecting PEG chains or mAb-PEG moieties
allows for the direct interaction of the cell penetrating peptide moiety with the cell membrane
(Reproduced from Sawant et al.
2006
with permission)
biotin residues at pH 7.4 when it is unionized, but take protons at pH 6.8-7.4,
stretch and expose biotin for interaction with cancer cells. The micelles also
showed pH-dependent dissociation, causing the enhanced release of DOX from the
carrier in early endosomal pH.
Double-targeted immunomicelles were developed by Torchilin et al. (Fig.
14
)
(Sawant et al.
2006
). The mixed micelles consisted of monoclonal antimyosin
antibody 2G4 conjugated to PEO-phosphatidylethanolamine (PEO-PE) via
p-Nitrophenylcarbonyl-PEO-PE (pNP-PEO-PE); nonspecific cell penetrating
peptide (e.g. TATp) or biotin attached to PE (TAT-PE or biotin-PE) or short
PEO-PE; and PEO-Hyd-PE. Under physiological pH, biotin and TATp on the
surface of nanocarriers were shielded by long protecting PEO chains or by even
longer pNP-PEO-PE used to attach antibodies to the nanocarrier. At pH 7.4-8.0,
micelles demonstrated high specific binding with 2G4 antibody substrate (myosin),
but very limited binding on biotin substrate (avidin) or internalization by NIH/3T3
or U-87 cells mediated by TATp on micelles. However, upon 15-30 min incubation
at pH 5.0-6.0, nanocarriers lost their protective PEO shell because of acidic hydro-
lysis of PEO-Hyd-PE and acquired the ability for strong interaction with an avidin
column or effective internalization by cells via TATp.
Fig. 13
(continued)
for 4 and 24 h. Confocal images of cells stained with MitoTracker
®
green (
green
)
and DAPI (
blue
) were then taken and the pictures were superimposed. Pink color shows localization
of DOX (
red
) in nucleus (
blue
), while yellow color is an indication for localization of DOX (
red
) in
mitochondria (
green
) or endo/lysosomes (Reproduced from Xiong et al.
2010a
with permission)
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