Biomedical Engineering Reference
In-Depth Information
10.3.2.2.1
“ Grafting to ” Method
PEG Coating with Silane as a Linker
One of the simplest ways to introduce PEG
onto MNPs was illustrated by the reaction of 10 nm MNPs (prepared by precipita-
tion from partially reduced ferric chloride aqueous solution) with methoxy- PEG -
silane in toluene [40] . This involved reaction of the silane group of methoxy - PEG - silane
with the hydroxyl group on the MNP surface. After 48 h of culture in a medium
supplemented with 0.2 mg ml
− 1
PEG - modifi ed nanoparticles, the morphology and
viability of both macrophages and breast cancer cells containing the modifi ed
nanoparticles were close to those of control cells, which suggested that the
nanoparticles were indeed biocompatible. However, the presence of PEG on the
nanoparticles affected their internalization by macrophages and cancer cells in
different ways. PEGylation was shown to enhance nanoparticle uptake into breast
cancer cells (BT20) compared to unmodifi ed nanoparticles, whereas the reverse
effect was true with macrophages. In a subsequent report [42], the authors referred
to a modifi cation of MNPs with a bifunctional silane-PEG-trifl uoroethylester
linker, followed by treatment with ethylenediamine and conjugation with folic acid
(FA) to the amino-termini of the PEG chains. A schematic of the immobilization
procedure is shown in Figure 10.3. The MNP-PEG-FA conjugates were shown to
be taken up by target cells at signifi cantly higher levels than were nontargeting
nanoparticles coated with PEG or dextran. The specifi city of MNP - PEG - FA to
target tumor cells was demonstrated by the increased nanoparticle uptake and
signifi cant contrast enhancement of HeLa cells (which are known to signifi cantly
overexpress the folate receptor) over MG-63 cells (which express very low levels of
the folate receptor). In subsequent studies, the same research group applied this
method again, but used a bifunctional silane - PEG - trifl uoroethylester linker to
immobilize the anticancer drug, methotrexate ( MTX ), onto MNPs [43] . Rat glioma
cells (9L) cultured in the presence of 0.1 mg ml
− 1
MNP - PEG - MTX exhibited a
marked reduction in viability. The cellular uptake of MNP- PEG - MTX was signifi -
Figure 10.3
The chemical reaction scheme for the synthesis of
NP-PEG-FA conjugates. Reprinted with permission from Ref.
[42]; © 2006, John Wiley & Sons, Inc.
