Topics in Current Chemistry (2020) 378:35
1 3
The potential of CQDs for use in diagnostic applications has increased recently
with the metal doping of NPs with N and lanthanides (e.g. Gd and Yb), resulting
in co-doped nanomaterials exhibiting not only strong fluorescence but also high
constrast capabilities in magnetic resonance imaging (MRI) and computed tomography (CT) [42]. This simple approach has enabled the design of multimodal QDs
for bioimaging applications. However, studies on the surface modification of these
co-doped NPs with appropriate recognition biomolecules (BMs) for targeted bioimaging are still needed.
3 Stabilization Strategies for QDs in Aqueous Media
As mentioned in a previous section, conventional high-quality fluorescent QDs are
commonly synthesized in organic solvents at high temperature. However, the QDs
must be made water-compatible (stable in aqueous and biological media so that they
maintain their optoelectronic properties) if the intenstion is to use them in bioanalytical applications. To this end, surface modification of the QDs after synthesis is
a must; as well, QDs should have functional groups available on their surface for
further bioconjugation to BMs.
The appropriate QD surface passivation also can solve some of the problems typically affecting these NPs. First, crystalline NPs can easily form surface defects that
quench the fluorescence properties of naked QDs [43]. Second, naked QDs can suffer from surface oxidation, photochemical degradation and/or the leaching of metal
ions from the NP core after exposure to ionic or biological media, which affects
their optoelectronic properties and produces undesirable cytotoxicity [44]. Thus,
modification of the QD surface with the appropriate ligands is essential not only to
stabilize the NPs in physiological media (particularly important if they are going
to be used in clinical applications) but also to reduce nanocrystal surface defects,
thereby minimizing QD reactivity and toxicity. Moreover, despite the significant
progress achieved in the synthesis of QDs, biological uses of QDs require that such
NPs be modified into biocompatible probes. In this context, the availability of robust
and versatile NP surface chemistries are invaluable strategies to achieve stabilization
of the QDs in biological buffers while preserving their original photophysical properties and providing adequate reactive groups for further bioconjugations. The three
main strategies employed for hydrophilization of QDs (based on the attachment of
polar functional groups to the surface of the QD) are summarized in Fig. 4.
As shown in Fig. 4, a universal and simple approach is based on ligand exchange
of the original hydrophobic coating of the QDs (e.g. trioctylphosphine oxide
[TOPO] chains). In this method, the original coating is removed and replaced with
bifunctional molecules that often bind to the QD surface (e.g. through a thiol end)
and which have a hydrophilic functional group on the other end (such as carboxyl or
sulfonic acids) that provides the required NP solubility in aqueous and polar media
and is also available for further bioconjugation [19]. Bidentate ligands, such as dithiothreitol (DTT) or dihydrolipoic acid (DHLA), as well as oligomeric phosphines,
peptides and crosslinked dendrons are widely used to obtain QDs that are stable in
an aqueous environment [45].
140
Reprinted from the journal
1 3
The potential of CQDs for use in diagnostic applications has increased recently
with the metal doping of NPs with N and lanthanides (e.g. Gd and Yb), resulting
in co-doped nanomaterials exhibiting not only strong fluorescence but also high
constrast capabilities in magnetic resonance imaging (MRI) and computed tomography (CT) [42]. This simple approach has enabled the design of multimodal QDs
for bioimaging applications. However, studies on the surface modification of these
co-doped NPs with appropriate recognition biomolecules (BMs) for targeted bioimaging are still needed.
3 Stabilization Strategies for QDs in Aqueous Media
As mentioned in a previous section, conventional high-quality fluorescent QDs are
commonly synthesized in organic solvents at high temperature. However, the QDs
must be made water-compatible (stable in aqueous and biological media so that they
maintain their optoelectronic properties) if the intenstion is to use them in bioanalytical applications. To this end, surface modification of the QDs after synthesis is
a must; as well, QDs should have functional groups available on their surface for
further bioconjugation to BMs.
The appropriate QD surface passivation also can solve some of the problems typically affecting these NPs. First, crystalline NPs can easily form surface defects that
quench the fluorescence properties of naked QDs [43]. Second, naked QDs can suffer from surface oxidation, photochemical degradation and/or the leaching of metal
ions from the NP core after exposure to ionic or biological media, which affects
their optoelectronic properties and produces undesirable cytotoxicity [44]. Thus,
modification of the QD surface with the appropriate ligands is essential not only to
stabilize the NPs in physiological media (particularly important if they are going
to be used in clinical applications) but also to reduce nanocrystal surface defects,
thereby minimizing QD reactivity and toxicity. Moreover, despite the significant
progress achieved in the synthesis of QDs, biological uses of QDs require that such
NPs be modified into biocompatible probes. In this context, the availability of robust
and versatile NP surface chemistries are invaluable strategies to achieve stabilization
of the QDs in biological buffers while preserving their original photophysical properties and providing adequate reactive groups for further bioconjugations. The three
main strategies employed for hydrophilization of QDs (based on the attachment of
polar functional groups to the surface of the QD) are summarized in Fig. 4.
As shown in Fig. 4, a universal and simple approach is based on ligand exchange
of the original hydrophobic coating of the QDs (e.g. trioctylphosphine oxide
[TOPO] chains). In this method, the original coating is removed and replaced with
bifunctional molecules that often bind to the QD surface (e.g. through a thiol end)
and which have a hydrophilic functional group on the other end (such as carboxyl or
sulfonic acids) that provides the required NP solubility in aqueous and polar media
and is also available for further bioconjugation [19]. Bidentate ligands, such as dithiothreitol (DTT) or dihydrolipoic acid (DHLA), as well as oligomeric phosphines,
peptides and crosslinked dendrons are widely used to obtain QDs that are stable in
an aqueous environment [45].
140
Reprinted from the journal