Biomedical Engineering Reference
In-Depth Information
cross-section, and high photostability. 27 To be used for biological applications,
different solubilization strategies for QDs have been developed over the past
decades 28-30 especially for use in fluorescent imaging in vitro and in vivo. In
most cases, these QDs are modified with thiol-containing compounds, such
as mercaptoacetic acid (dihydrolipoic acid derivatives), or more sophisticated
compounds such as alkylthiol-terminated DNA, thioalkylated oligoethylene-
glycols, D,L-cysteine, poly(ethylene glycol) (PEG)-terminated dihydrolipoic
acid having significant in vitro and in vivo stability. 31-33 Encapsulation in a
layer of amphiphilic diblock or triblock copolymers, phospholipid micelles,
silica shells, or amphiphilic polysaccharides, polymer shells, oligomeric phos-
phine coating, or by phytochelatin-peptides coating or histidine-rich proteins
is another QD solubilization technique. 34-36 The modified water soluble QDs
can be covalently linked with biorecognition molecules such as peptides, anti-
bodies, nucleic acids, or small-molecule ligands for use as biological labels
in molecular and cellular imaging. 37-41 Biological applications of QDs include
fluorescence imaging, immunoassays, DNA assay, fluorescence labeling of cel-
lular proteins, cell tracking, pathogen and toxin detection, and in vivo animal
imaging.
The most extensively studied QDs are the cadmium containing NMs CdSe
or CdTe core or core/shell that are encapsulated in various coatings. 42 QDs are
NMs, which are semiconductor metalloid-crystal structures of approximately
2-100 nm, containing about 200-10,000 atoms. 43,44 QDs have unique optical
and electronic properties including high brightness and stable fluorescence that
are dependent upon their nanometer size. QDs are brighter than organic dyes
and are more stable. The large surface area to volume ratio that is imparted by
the small size makes QDs easy to functionalize with different biomolecules for
various applications. These properties provide QDs the potential for biologi-
cal imaging, cancer detection and imaging, 43 drug, 45 and vaccine delivery, 46 as
well as immunotherapy and hyperthermia. 44,47 However, the cadmium content
of QDs dampens the enthusiasm for its biomedical significance because little is
known about the health risks of exposure to cadmium containing NMs. 42
The most significant and also the most exploited feature of QDs is their
size-tunable fluorescence. The bandgap energy, which is the minimum energy
required to excite an electron to an energy level above its ground state, is a fixed
entity that is unique to the nature of the semiconductor material 42,44 and fluores-
cence is the result of relaxation of the excited electron back to its ground state
through the emission of a photon. When an incoming photon of energy that is
greater than the bandgap of the material is absorbed, an electron is excited from
the valence band to the conduction band, creating a hole in the valence band. 48
As the electron relaxes back down to the valence band, a photon that has energy
proportional to the bandgap of the material is emitted. Unlike fluorescent organic
dyes, QDs can absorb at a broad range of wavelengths of light greater than its
bandgap and emit at a specific wavelength because of this process. As the size of
a particle decreases to the nanoscale (less than the Bohr radius of the material),
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