Biomedical Engineering Reference
In-Depth Information
ligands and recognition peptides, can also be attached onto NPs in order to
label cell-membrane proteins. For instance, folic acid was attached to dye-
doped silica NPs and targeted to SCC-9 cancer cells, which over-express
folate receptors [168].
Peptide-targeted uptake is another efficient technique for cancer cell im-
aging. This technique is based on the propensity of the cells to recognize
and internalize NPs labeled with specific peptides, and even deliver them to
specific cellular compartments. Human lung adenocarcinoma (A549) cells
(in vitro) and rat brain tissue (in vivo) were successfully labeled using TAT-
labeled NPs. Using this strategy, diagnostic and therapeutic agents can be
delivered to the biological target of interest [168]. Recently, aptamers have
emerged as a novel class of ligands. Aptamers are short strands of DNA/
RNA for recognition of a variety of targets, including proteins and small
molecules, as well as complex samples. Aptamers have significant advantages
over antibodies and peptides, including high affinity, excellent specificity,
and lack of immunogenicity. Specific targeting of acute leukemia cells with
aptamer-conjugated NPs has been developed using fluorescence microscopy
or flow cytometry [169]. NP-aptamer conjugates greatly increase the fluo-
rescence signal from the cell. This property shows the potential applications
of silica NPs in the elucidation of cells with low densities of aptamer binding
sites, or with relatively weak binding probes where the fluorescence signal
from the fluorophore is too weak for observation [170]. Tris(2,2'-bipyridyl)
dichlororuthenium(II) hexahydrate (RuBpy)-doped silica NPs have been
used as highly sensitive and photostable labels in Affymetrix GeneChips
technology. Biotin-labeled cRNA samples from a human lung cancer cell
line were hybridized on the arrays, and then incubated with streptavidin and
staining with PEG-biotin-labeled NPs. Even with the present unfavorable
imaging modality and existing optical excitation and detection systems of the
GeneChips, the fluorescent silica NPs were demonstrated to be superior to
the traditional streptavidin-phycoerythrin (SAPE). Fluorescent silica NPs
can act as nonviral vectors for gene delivery and biophotonics methods, and
may be used to optically monitor intracellular trafficking and gene transfec-
tion. The potential of cationic silica NPs was investigated for in vivo gene
transfer [171]. The NPs were tested for their ability to transfer genes in vivo
in the mouse lung, and a two-fold increase in the expression levels was found
with silica particles in comparison to enhanced green fluorescent protein
(EGFP) alone. Silica NPs are also promising candidates for improved drug
delivery systems because of their intrinsic hydrophilicity, biocompatibility,
and nontoxicity, as well as the excellent protection they provide for their
encapsulated drugs. With drug molecules loaded into silica NPs, surface
modification of the NPs with bio-recognition entities can allow specific cells
or receptors in the body to be located. Upon target recognition, NPs can
then release their drug payload at a rate precisely controlled by tailoring the
internal structure of the particles according to a desired diffusion (release)
