employed to make a quantum dots [85]. Structurally, QDs are comprised of a
shell-coated semiconductor core, and a capping agent to improve water solubility.
The QDs core, usually made from cadmium selenide (CdSe), absorbs incident
photons generating electron-hole pairs that rapidly recombine emitting a photon of
less energy [86]. The quantum confinement, or physical confinement of excitons,
presents QDs with many unique features that favor their biological use over conventional fluorophores for fluorescence imaging [87]. Conventional dye molecules,
such as organic dyes or fluorescent proteins, present major limitations, including
poor photostability that can result in photobleaching, as well as phototoxicity
through the production of toxic radicals that prevents long-term visualization of
labeled compounds in living cells [88]. Photostable QDs, on the other hand, are
advantageous for having size- and composition-tunable emission from visible to
infrared wavelengths, large absorption coefficients and high levels of brightness
[84]. Moreover, QDs can be used for combinatorial optical encoding [89], a
technique that makes use of a large amount of fluorophores that are combine to
encode several molecules at the same time; or multiplex imaging, in which QD is
targeted to specific tissues that can be imaged at the same time, since (i) a single
wavelength of excitation can be used to concurrently excite multiple probes of
different emissions (ii) size and composition can be tuned to make QDs with a wide
range of absorption and emission wavelengths from the visible to NIR regions [87,
89, 90]. The QDs size can be tuned by various methods; for example, through the
Ostwald ripening process in which the growth rate is dependent on both the temperature and the amount of limiting reagent [91]. The shape of QDs can also be
controlled, and more information about synthesis parameters can be found in the
literature [92]. For more information about the types and applications of QDs as
biological imaging agents, including for optical imaging technology, please refer to
literature [93–96].
To make QDs water soluble, which is important when considering biological
applications, QDs are often encapsulated by amphiphilic molecules, such as PEG,
triblock copolymers, octylamine-modified polyacrylic acid, oligomeric phosphine
and copolymers of alkyl monomers and anhydrides [97]. Functionalization of QDs
with several molecules, such as nucleic acids, peptides, proteins, antibodies, and
enzymes have been reported [23]. Detailed information regarding QDs’ surface
modification and conjugation with biomolecules can be found here [23, 98, 99].
Since optical imaging is mainly limited by poor tissue penetration even in the
NIR (700- 900 nm) window, QD-based materials have been explored as potential
imaging agents for both SPECT and PET. Felber et al. [100] attempted to radiolabel
QDs with [
99m Tc(OH 2 ) 3 (CO) 3 ]
+ using a new coating ligand containing a terminal
thiol group, a PEG linker and 2,3-diaminopropionic acid (DAP) chelator
(HS-PEG-DAP) and although the radiolabeling yield was high ( ! 95%), the
complex was unstable in serum and coating ligand detachment was found, in which
the quantum yield decreased from 10 to 7% after one week. In contrast, Park et al.
[101] investigated the possibility of radioiodination of QDs using Bolton-hunter
reagent. The authors were able to successfully radiolabeled QDs using
24
C. A. Ferreira et al.
shell-coated semiconductor core, and a capping agent to improve water solubility.
The QDs core, usually made from cadmium selenide (CdSe), absorbs incident
photons generating electron-hole pairs that rapidly recombine emitting a photon of
less energy [86]. The quantum confinement, or physical confinement of excitons,
presents QDs with many unique features that favor their biological use over conventional fluorophores for fluorescence imaging [87]. Conventional dye molecules,
such as organic dyes or fluorescent proteins, present major limitations, including
poor photostability that can result in photobleaching, as well as phototoxicity
through the production of toxic radicals that prevents long-term visualization of
labeled compounds in living cells [88]. Photostable QDs, on the other hand, are
advantageous for having size- and composition-tunable emission from visible to
infrared wavelengths, large absorption coefficients and high levels of brightness
[84]. Moreover, QDs can be used for combinatorial optical encoding [89], a
technique that makes use of a large amount of fluorophores that are combine to
encode several molecules at the same time; or multiplex imaging, in which QD is
targeted to specific tissues that can be imaged at the same time, since (i) a single
wavelength of excitation can be used to concurrently excite multiple probes of
different emissions (ii) size and composition can be tuned to make QDs with a wide
range of absorption and emission wavelengths from the visible to NIR regions [87,
89, 90]. The QDs size can be tuned by various methods; for example, through the
Ostwald ripening process in which the growth rate is dependent on both the temperature and the amount of limiting reagent [91]. The shape of QDs can also be
controlled, and more information about synthesis parameters can be found in the
literature [92]. For more information about the types and applications of QDs as
biological imaging agents, including for optical imaging technology, please refer to
literature [93–96].
To make QDs water soluble, which is important when considering biological
applications, QDs are often encapsulated by amphiphilic molecules, such as PEG,
triblock copolymers, octylamine-modified polyacrylic acid, oligomeric phosphine
and copolymers of alkyl monomers and anhydrides [97]. Functionalization of QDs
with several molecules, such as nucleic acids, peptides, proteins, antibodies, and
enzymes have been reported [23]. Detailed information regarding QDs’ surface
modification and conjugation with biomolecules can be found here [23, 98, 99].
Since optical imaging is mainly limited by poor tissue penetration even in the
NIR (700- 900 nm) window, QD-based materials have been explored as potential
imaging agents for both SPECT and PET. Felber et al. [100] attempted to radiolabel
QDs with [
99m Tc(OH 2 ) 3 (CO) 3 ]
+ using a new coating ligand containing a terminal
thiol group, a PEG linker and 2,3-diaminopropionic acid (DAP) chelator
(HS-PEG-DAP) and although the radiolabeling yield was high ( ! 95%), the
complex was unstable in serum and coating ligand detachment was found, in which
the quantum yield decreased from 10 to 7% after one week. In contrast, Park et al.
[101] investigated the possibility of radioiodination of QDs using Bolton-hunter
reagent. The authors were able to successfully radiolabeled QDs using
24
C. A. Ferreira et al.