Direct Deposition of Nanomaterials onto Cells - Cell Surface Engineering: Fabrication of Functional Nanoshells - page 38

nanoparticles depends on the nanoparticles surface charge. Positively
charged gold nanoparticles modified by [N,N,N-trimethyl (11-mercaptoun-
decyl) ammonium] showed the tendency to pass through the fluid phase of
the lipid membrane and became trapped between the hydrophobic bilayers
while mercaptoundecanoic-acid-coated gold particles, which had a negative
charge, did not penetrate the lipid membrane. 25
Another research group proposed a new technique to study the ad-
sorption/internalization process of gold nanoparticles (AuNP) onto the cells
depending on their surface charges. Neutral, positive, and negatively
charged gold nanoparticles (modified with poly(vinyl alcohol),
poly(allylamine hydrochloride) polymers, and citric acid, respectively) were
incubated with breast cancer cells (SK-BR-3) followed by treatment with an
etching solution containing I 2 and KI at low molar concentrations so that it
could selectively dissolve AuNPs on the cell surface without killing the cells.
The results indicate that the uptake and adsorption onto the surface for
positively charged gold nanospheres was much higher than for neutral or
negatively charged ones. 26 These studies show that the process of nano-
material deposition can be regulated through the surface chemistry of both
components in the deposition process. Factors like the z-potential of the cell
membrane, the chosen nanomaterials, and the ionic strength/pH of the
medium, seem to play an important role in selective modification of the cell
surface with nanomaterials.
The cell plasma membrane contains several extracellular structures in-
cluding receptors, channels, and glycocalyx that can be used as targets for
selective nanoparticles deposition. Cell surface receptors regulate com-
munication between the cell and its environment through extracellular
signaling ligands which bind to the receptor and trigger intracellular
changes. Thus, a receptor may serve as an anchor for ligand-functionalized
nanoparticle attachment. Click and surface chemistry methods allow one to
e ciently conjugate biomacromolecules to the surface of nanoparticles for
further deposition onto the cell surface receptors. For example, magnetic
nanoparticles were covalently coupled to the metal-binding proteins lacto-
ferrin and ceruloplasmin for targeting cell surface receptors (Figure 3.5a).
On human dermal fibroblasts, it was shown that protein functionalized
particles were attached to the cell membrane due to ligand-receptor inter-
actions (Figure 3.5c and d) while bare magnetic nanoparticles were in-
ternalized into the cytoplasm possibly via endocytosis (Figure 3.5a). The
overexpression of the receptors for these ligands on the mammalian cells led
to a homogeneous and quite dense distribution of magnetic nanoparticles
on the cell surface. 27
In another experiment, urokinase plasminogen activator receptor (uPAR),
the specific surface biomarker of several types of cancer, was targeted by
modified magnetic nanoparticles. For this purpose, the stabilizing oleic acid
coating of the magnetic nanoparticles was first replaced by silane amine
(3-aminopropyl-trimethoxysilane) and reacted with NHS-PEG-N 3 (N-Hydroxy-
succinimide-polyethylene glycol-azide)

d n 8 y 4 n g | 8

.

thereby providing azide groups