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Topics in Current Chemistry (2020) 378:35
All of the recent advances in bioconjugation chemistry has made it possible
to attach almost any BM of interest to the surface of a QD. However, work is
till needed to further enhance the development and applications of QD bioconjugates. In this context, we have identified the following issues.
The orientation of the BMs is a key issue that still needs to be addressed. Many
often random orientations are sufficient when the QDs are used in conventional
hybridization applications. However, controlled orientations may be needed for
the assembly of functionalized 3D structures.
The functionalization of QDs with different BMs (e.g. antibodies, peptides,
nucleic acids or aptamers) offer a wide range of opportunities for applying the
nanoassemblies in clinical diagnosis, including ultrasensitive detection of disease
biomarkers, in vivo targeted imaging or drug delivery applications. The multiplexing capabilities of these QDs open new avenues for the use of differently
sized QDs for the simultaneous detection of multiple biomarkers (a key aspect
in efficient clinical diagnosis). Moreover, encapsulation of multiple QDs in highvolume nanocarriers (e.g. nanosomes or PLGA NPs) may enable the construction
of a panel of multifunctional systems for targeted drug delivery and molecular
imaging.
The development of new multimodal imaging nanoprobes is a focus of many
researchers. The use of NPs as imaging probes offers several advantages over conventional molecular-scale contrast agents; these include high loading capacity,
where the concentration of the imaging agents can be controlled within each NP
during the synthesis process; tunable surface that can potentially extend the circulation time of the contrast agents in the blood or target them to specific locations in
the body; or provision of multimodal imaging capacities because NPs can combine
two or more contrast properties, which can be used in multiple imaging techniques
simultaneously [160]. Recent advances in nanotechnology has enabled the development of multifunctional QDs by doping the nanocrystals with appropriate metals, thus integrating two or more imaging contrast agents and thereby enabling their
detection by different imaging techniques [42].
One of the major challenges when developing novel bioassay methods for clinical applications is the requirement for high sensitivity in the detection because of
the ultralow concentrations of the biomarkers to be detected. Here, the use of QDs
as tags in immunoassays could be a powerful approach to achieve the desired ultrasensitivity. As an example, ultrahigh sensitivity for BMs could be easily achieved
through metal deposition on the surface of the NP tags acting as catalytic seeds, thus
effectively amplifying the size of the metallic NPs after the immunoassay [161].
Obviously, QDs cannot be safely used as tags for in vivo applications until the
problem of their toxicity is solved. Despite very extensive studies of toxicity of
QDs in different cellular and animal models, the in vivo toxicological effect of QDs
remains controversial [37]. The possible release of toxic heavy metals from the core
of the QDs as a result of intensive UV illumination has to be taken into account
[44]. The preparation of heavy metal-free QDs is being addressed as a promising
avenue to overcome such toxicity problems. Additionally, it must be considered that
an ideal solubilization strategy should reduce QD toxicity and undesirable nonspecific QD uptake by living tissues, thus reducing cytotoxic effects.
167
Reprinted from the journal
Topics in Current Chemistry (2020) 378:35
All of the recent advances in bioconjugation chemistry has made it possible
to attach almost any BM of interest to the surface of a QD. However, work is
till needed to further enhance the development and applications of QD bioconjugates. In this context, we have identified the following issues.
The orientation of the BMs is a key issue that still needs to be addressed. Many
often random orientations are sufficient when the QDs are used in conventional
hybridization applications. However, controlled orientations may be needed for
the assembly of functionalized 3D structures.
The functionalization of QDs with different BMs (e.g. antibodies, peptides,
nucleic acids or aptamers) offer a wide range of opportunities for applying the
nanoassemblies in clinical diagnosis, including ultrasensitive detection of disease
biomarkers, in vivo targeted imaging or drug delivery applications. The multiplexing capabilities of these QDs open new avenues for the use of differently
sized QDs for the simultaneous detection of multiple biomarkers (a key aspect
in efficient clinical diagnosis). Moreover, encapsulation of multiple QDs in highvolume nanocarriers (e.g. nanosomes or PLGA NPs) may enable the construction
of a panel of multifunctional systems for targeted drug delivery and molecular
imaging.
The development of new multimodal imaging nanoprobes is a focus of many
researchers. The use of NPs as imaging probes offers several advantages over conventional molecular-scale contrast agents; these include high loading capacity,
where the concentration of the imaging agents can be controlled within each NP
during the synthesis process; tunable surface that can potentially extend the circulation time of the contrast agents in the blood or target them to specific locations in
the body; or provision of multimodal imaging capacities because NPs can combine
two or more contrast properties, which can be used in multiple imaging techniques
simultaneously [160]. Recent advances in nanotechnology has enabled the development of multifunctional QDs by doping the nanocrystals with appropriate metals, thus integrating two or more imaging contrast agents and thereby enabling their
detection by different imaging techniques [42].
One of the major challenges when developing novel bioassay methods for clinical applications is the requirement for high sensitivity in the detection because of
the ultralow concentrations of the biomarkers to be detected. Here, the use of QDs
as tags in immunoassays could be a powerful approach to achieve the desired ultrasensitivity. As an example, ultrahigh sensitivity for BMs could be easily achieved
through metal deposition on the surface of the NP tags acting as catalytic seeds, thus
effectively amplifying the size of the metallic NPs after the immunoassay [161].
Obviously, QDs cannot be safely used as tags for in vivo applications until the
problem of their toxicity is solved. Despite very extensive studies of toxicity of
QDs in different cellular and animal models, the in vivo toxicological effect of QDs
remains controversial [37]. The possible release of toxic heavy metals from the core
of the QDs as a result of intensive UV illumination has to be taken into account
[44]. The preparation of heavy metal-free QDs is being addressed as a promising
avenue to overcome such toxicity problems. Additionally, it must be considered that
an ideal solubilization strategy should reduce QD toxicity and undesirable nonspecific QD uptake by living tissues, thus reducing cytotoxic effects.
167
Reprinted from the journal