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Topics in Current Chemistry (2020) 378:35
quantum yields than organic fluorophores. Consequently, fluorescent NPs are
nearly 20-fold brighter and many thousand-fold more stable against photobleaching than conventional organic dyes [19, 20]. Such exceptional optical behavior
justifies the rapid emergence of QDs as valuable photoluminescent probes in
many analytical applications.
In particular, the use of NPs for diagnostic purposes is increasing exponentially
due to their highly valuable optoelectronic properties and small size. Additionally,
recent advances in such areas as surface modification and functionalization have
given rise to the improved colloidal stability of NPs in complex media and biological buffers and biocompatibility, while allowing the NPs to bond to recognition elements [21]. In this context, especially relevant are the developments in the synthesis
of NPs with interesting optical properties that overcome the limitations of traditional
organic dyes, including the synthesis of gold NPs (AuNPs), semiconductor QDs,
gold nanoclusters, silver nanoclusters, rare-earth-based NPs, carbon dots and dyeloaded NPs [22].
However, despite the exceptional properties demonstrated by QDs developed to
date, their applications in clinical analysis, especially during the first decades of
development, can still be considered to be somehow limited, in part due to their
low targeting efficiency and eventual high toxicity, both of which could hinder their
application in in vivo imaging. These limitations underlie the many research efforts
to develop QDs exhibiting low biological toxicity (e.g. those based on an Ag 2 S core)
[23]. Additionally, in the absence of any molecular moiety being attached to the NP
surface, QDs generally show nonselective distribution acros different organisms,
thus failing to satisfy the minimum requirements for appropriate molecular imaging.
Clearly, the development of QD-based nanoprobes requires a previous surface functionalization of the NPs to facilitate the various approaches used in targeting-guided
imaging techniques. In addition, to ensure the required biocompatibility of the nanoprobes to be used in in vivo imaging or sensing, an appropriate surface functionalization of the NPs is required.
The aim of this review is to highlight advances in the use of QDs in diagnostic
applications. In the following sections, we first introduce and briefly describe the
main types of QDs used in bioanalysis. This is followed by a section that focuses
on the strategies of solubilization and stabilization of QDs in aqueous solutions
under physiological conditions and then by a section in which approaches used for
the functionalization of QDs with biological molecules are summarized. The functionalization of QDs is a key aspect of their use and a requirement before they can
be employed for the detection of analytes in biological matrices. Thereafter, we
describe some of the most relevant applications of QD bioconjugates in the optical imaging of biomarkers, including a review of the in vitro applications of QDs
in medicine in which different detection schemes based on the bioconjugation of
QDs to antibodies, aptamers, peptides or other types of recognition elements. In
this context, we provide an overview of recent advances in the development of lowcost, portable and easy-to-use QD-based biosensing devices for clinical applications
(point-of-care). The final section discusses future prospects with the intention to
indicate the direction that research on the use of QDs in diagnostic applications is
heading.
135
Reprinted from the journal
Topics in Current Chemistry (2020) 378:35
quantum yields than organic fluorophores. Consequently, fluorescent NPs are
nearly 20-fold brighter and many thousand-fold more stable against photobleaching than conventional organic dyes [19, 20]. Such exceptional optical behavior
justifies the rapid emergence of QDs as valuable photoluminescent probes in
many analytical applications.
In particular, the use of NPs for diagnostic purposes is increasing exponentially
due to their highly valuable optoelectronic properties and small size. Additionally,
recent advances in such areas as surface modification and functionalization have
given rise to the improved colloidal stability of NPs in complex media and biological buffers and biocompatibility, while allowing the NPs to bond to recognition elements [21]. In this context, especially relevant are the developments in the synthesis
of NPs with interesting optical properties that overcome the limitations of traditional
organic dyes, including the synthesis of gold NPs (AuNPs), semiconductor QDs,
gold nanoclusters, silver nanoclusters, rare-earth-based NPs, carbon dots and dyeloaded NPs [22].
However, despite the exceptional properties demonstrated by QDs developed to
date, their applications in clinical analysis, especially during the first decades of
development, can still be considered to be somehow limited, in part due to their
low targeting efficiency and eventual high toxicity, both of which could hinder their
application in in vivo imaging. These limitations underlie the many research efforts
to develop QDs exhibiting low biological toxicity (e.g. those based on an Ag 2 S core)
[23]. Additionally, in the absence of any molecular moiety being attached to the NP
surface, QDs generally show nonselective distribution acros different organisms,
thus failing to satisfy the minimum requirements for appropriate molecular imaging.
Clearly, the development of QD-based nanoprobes requires a previous surface functionalization of the NPs to facilitate the various approaches used in targeting-guided
imaging techniques. In addition, to ensure the required biocompatibility of the nanoprobes to be used in in vivo imaging or sensing, an appropriate surface functionalization of the NPs is required.
The aim of this review is to highlight advances in the use of QDs in diagnostic
applications. In the following sections, we first introduce and briefly describe the
main types of QDs used in bioanalysis. This is followed by a section that focuses
on the strategies of solubilization and stabilization of QDs in aqueous solutions
under physiological conditions and then by a section in which approaches used for
the functionalization of QDs with biological molecules are summarized. The functionalization of QDs is a key aspect of their use and a requirement before they can
be employed for the detection of analytes in biological matrices. Thereafter, we
describe some of the most relevant applications of QD bioconjugates in the optical imaging of biomarkers, including a review of the in vitro applications of QDs
in medicine in which different detection schemes based on the bioconjugation of
QDs to antibodies, aptamers, peptides or other types of recognition elements. In
this context, we provide an overview of recent advances in the development of lowcost, portable and easy-to-use QD-based biosensing devices for clinical applications
(point-of-care). The final section discusses future prospects with the intention to
indicate the direction that research on the use of QDs in diagnostic applications is
heading.
135
Reprinted from the journal