stability and photostability; relatively small size; and absence of toxic metallic
elements. So far, the methods for the preparation of NIR-II QDs can be mainly
divided into two major strategies: the organometallic route and aqueous synthesis
approaches [72–75]. Different reaction conditions, such as temperature, hot injection
time, precursor reagents, and exchange ligands, have been utilized to prepare NIR-II
QDs with diverse components. As QDs synthesized in the organic phase usually
have very poor water solubility and biocompatibility, the synthesis of QDs in
aqueous solution has become an alternative option, which also has the advantages
of convenience, easy control, reproducibility, low cost, and large-scale preparation.
Because of the poor crystal quality with nonuniform particle size, broad spectra, and
low QYs of the resulting QDs, this method still requires improvement. Great efforts
have been made toward water solubilization and biofunctionalization of chemically
synthesized QDs. The employment of biological systems as the reaction platforms
has three distinctive features: (1) intrinsic generation of metal-reducing and metalbinding agents with the capability of reducing metal ions, (2) easy modulation of the
platform by means of genetic engineering for the expression of specific biomolecules
to regulate the QD growth and fluorescence emission, and (3) moderate reaction
conditions without the involvement of high-temperature and rigorous deoxygenation. In general, the biocompatible QDs may be prepared through three different
approaches: (1) using living organisms ranging from prokaryotes to eukaryotes as
the bioreactors, (2) using of either artificial cellular structures or functional biomolecules as the templates, and (3) surface modification of QDs. Among them, the
biosynthesis approach provides a green route to prepare biocompatible QDs without
the involvement of harsh reaction conditions or toxic chemicals.
4.3 Application In Vivo
In quantum dots in types III–V, InAs and InGa are the two typical ones possessing
outstanding optical properties as well as significantly lower intrinsic toxicity compared to other NIR QDs containing elements such as mercury or lead. So, they have
played an important role in biomedical and bioanalytical application. For example,
Bawendi has reported a class of high-quality NIR-II-emissive indium-arsenidebased quantum dots that are readily modifiable for various functional imaging
applications and that exhibit narrow and size-tunable emission and a dramatically
higher emission quantum yield than previously described NIR-II probes (Fig. 17)
[71]. To demonstrate the unprecedented combination of deep penetration, high
spatial resolution, multicolor imaging, and fast acquisition speed afforded by the
NIR-II quantum dots, they quantified, in mice, the metabolic turnover rates of
lipoproteins in several organs simultaneously and in real time, as well as heartbeat
and breathing rates in awake and unrestrained animals, and generated detailed threedimensional quantitative flow maps of the mouse brain vasculature.
Ag 2 S is a promising NIR-II fluorescent QD in the preclinical research because of
its nontoxic heavy metal and high uptake in tumors (Fig. 18e) [19]. In surgical
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S. He and Z. Cheng
elements. So far, the methods for the preparation of NIR-II QDs can be mainly
divided into two major strategies: the organometallic route and aqueous synthesis
approaches [72–75]. Different reaction conditions, such as temperature, hot injection
time, precursor reagents, and exchange ligands, have been utilized to prepare NIR-II
QDs with diverse components. As QDs synthesized in the organic phase usually
have very poor water solubility and biocompatibility, the synthesis of QDs in
aqueous solution has become an alternative option, which also has the advantages
of convenience, easy control, reproducibility, low cost, and large-scale preparation.
Because of the poor crystal quality with nonuniform particle size, broad spectra, and
low QYs of the resulting QDs, this method still requires improvement. Great efforts
have been made toward water solubilization and biofunctionalization of chemically
synthesized QDs. The employment of biological systems as the reaction platforms
has three distinctive features: (1) intrinsic generation of metal-reducing and metalbinding agents with the capability of reducing metal ions, (2) easy modulation of the
platform by means of genetic engineering for the expression of specific biomolecules
to regulate the QD growth and fluorescence emission, and (3) moderate reaction
conditions without the involvement of high-temperature and rigorous deoxygenation. In general, the biocompatible QDs may be prepared through three different
approaches: (1) using living organisms ranging from prokaryotes to eukaryotes as
the bioreactors, (2) using of either artificial cellular structures or functional biomolecules as the templates, and (3) surface modification of QDs. Among them, the
biosynthesis approach provides a green route to prepare biocompatible QDs without
the involvement of harsh reaction conditions or toxic chemicals.
4.3 Application In Vivo
In quantum dots in types III–V, InAs and InGa are the two typical ones possessing
outstanding optical properties as well as significantly lower intrinsic toxicity compared to other NIR QDs containing elements such as mercury or lead. So, they have
played an important role in biomedical and bioanalytical application. For example,
Bawendi has reported a class of high-quality NIR-II-emissive indium-arsenidebased quantum dots that are readily modifiable for various functional imaging
applications and that exhibit narrow and size-tunable emission and a dramatically
higher emission quantum yield than previously described NIR-II probes (Fig. 17)
[71]. To demonstrate the unprecedented combination of deep penetration, high
spatial resolution, multicolor imaging, and fast acquisition speed afforded by the
NIR-II quantum dots, they quantified, in mice, the metabolic turnover rates of
lipoproteins in several organs simultaneously and in real time, as well as heartbeat
and breathing rates in awake and unrestrained animals, and generated detailed threedimensional quantitative flow maps of the mouse brain vasculature.
Ag 2 S is a promising NIR-II fluorescent QD in the preclinical research because of
its nontoxic heavy metal and high uptake in tumors (Fig. 18e) [19]. In surgical
104
S. He and Z. Cheng