Topics in Current Chemistry (2020) 378:35
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Conversely, QDs active transportation is characterized by ligand–receptor-mediated transportation using ligands, such as peptides, proteins or antibodies. In addition, QD surface engineering is critical to minimize undesired nonspecific binding
adsorptions of QD probes in biological media. Surface functionalization of QDs
with uncharged hydrophilic moieties (e.g. PEG) or with zwitterion molecules produces highly water-stable nanoprobes while efficiently eliminating nonspecific binding (typically brought about by hydrophobic and/or pure electrostatic interactions).
The use of antibody–QD conjugates for guided-target labeling is probably the
most commonly used strategy in molecular imaging, although targeting can also be
achieved via bioconjugation of the QDs with peptides, DNA, modified proteins, etc.
Actually, a single QD (depending on its size) can be simultaneously conjugated with
several proteins and peptides [146]. It is well known that peptides are efficient carriers of QDs inside living cells. Therefore, peptide-modified QDs conjugates have
been widely used to target cellular BMs, including growth factor receptors, G protein-coupled receptors, integrins and even ion channels [147].
Moreover, small BMs can be also bioconjugated to QDs for in vitro imaging.
This is the case of aptamers, which are nucleic acid species that have been engineered to bind to various molecular targets, such as small molecules, proteins,
nucleic acids and even cells, tissues and organisms [148]. As an illustration, in one
study ZnS/CdSe fluorescent QDs were surface modified with PEG (for aqueous stabilization and biocompatibility) and streptavidine (to further bioconjugate the NP to
an appropriate BM receptor) [149]. The streptavidine–PEG–QD was then labeled
via streptavidine–biotin with a biotinylated aptamer that can specially bind the epidermal growth factor receptor varient III (EGFRvIII), which is specially distributed
on the surface of glioma cells. This labeled aptamer (QD-Apt) nanoprobe was then
employed in a fluorescence-guided surgery to allow safe resection of glioma [149].
In this study, the biodistribution of the QD-Apt nanoprobe and the capabilities of
targeted imaging of glioma in situ using orthotopic glioma models were evaluated.
Different studies were carried out, including an evaluation of the capability of the
QD-Apt to image U87-EGFRvIII (a human primary glioblastoma cell line [U87]
that overexpresses EGFRvIII) tumor areas. At 4 weeks of tumor development, a
whole-body fluorescence imaging examination was performed in different mice after
QDs (not bioconjugated) or QD-Apt were injected via the tail vein for 6 h. As can
be seen in Fig. 16, the image of the mice harboring the tumor which were administered the QD-Apt (group 1) had strong fluorescence signals in tumor areas, while the
group administered QDs (group 2) had no obvious fluorescence signals in the tumor
region. In addition, the mice having U87 tumors (groups 3 and 4) had no significant
fluorescence in tumor areas, regardless of whether they were administered QD-Apt
or QDs. In brief, the developed nanoprobe (QD-Apt) hasa great potential as a novel
fluorescence contrast agent for the molecular diagnosis, image-guided surgery, and
postoperative examination of gliomas.
Clearly, engineering more compact nanoprobes for fluorescence imaging is currently a research area of great practical interest. A key aspect in this reasearch area is
to try to enhance the final uptake of the QD-based nanoprobes in the cellular media.
To achieve this goal, much effort is directed towards avoiding (or reducing) eventual
QD aggregation or deposition in endosomes or lysosomes. In addition, studies to
162
Reprinted from the journal
1 3
Conversely, QDs active transportation is characterized by ligand–receptor-mediated transportation using ligands, such as peptides, proteins or antibodies. In addition, QD surface engineering is critical to minimize undesired nonspecific binding
adsorptions of QD probes in biological media. Surface functionalization of QDs
with uncharged hydrophilic moieties (e.g. PEG) or with zwitterion molecules produces highly water-stable nanoprobes while efficiently eliminating nonspecific binding (typically brought about by hydrophobic and/or pure electrostatic interactions).
The use of antibody–QD conjugates for guided-target labeling is probably the
most commonly used strategy in molecular imaging, although targeting can also be
achieved via bioconjugation of the QDs with peptides, DNA, modified proteins, etc.
Actually, a single QD (depending on its size) can be simultaneously conjugated with
several proteins and peptides [146]. It is well known that peptides are efficient carriers of QDs inside living cells. Therefore, peptide-modified QDs conjugates have
been widely used to target cellular BMs, including growth factor receptors, G protein-coupled receptors, integrins and even ion channels [147].
Moreover, small BMs can be also bioconjugated to QDs for in vitro imaging.
This is the case of aptamers, which are nucleic acid species that have been engineered to bind to various molecular targets, such as small molecules, proteins,
nucleic acids and even cells, tissues and organisms [148]. As an illustration, in one
study ZnS/CdSe fluorescent QDs were surface modified with PEG (for aqueous stabilization and biocompatibility) and streptavidine (to further bioconjugate the NP to
an appropriate BM receptor) [149]. The streptavidine–PEG–QD was then labeled
via streptavidine–biotin with a biotinylated aptamer that can specially bind the epidermal growth factor receptor varient III (EGFRvIII), which is specially distributed
on the surface of glioma cells. This labeled aptamer (QD-Apt) nanoprobe was then
employed in a fluorescence-guided surgery to allow safe resection of glioma [149].
In this study, the biodistribution of the QD-Apt nanoprobe and the capabilities of
targeted imaging of glioma in situ using orthotopic glioma models were evaluated.
Different studies were carried out, including an evaluation of the capability of the
QD-Apt to image U87-EGFRvIII (a human primary glioblastoma cell line [U87]
that overexpresses EGFRvIII) tumor areas. At 4 weeks of tumor development, a
whole-body fluorescence imaging examination was performed in different mice after
QDs (not bioconjugated) or QD-Apt were injected via the tail vein for 6 h. As can
be seen in Fig. 16, the image of the mice harboring the tumor which were administered the QD-Apt (group 1) had strong fluorescence signals in tumor areas, while the
group administered QDs (group 2) had no obvious fluorescence signals in the tumor
region. In addition, the mice having U87 tumors (groups 3 and 4) had no significant
fluorescence in tumor areas, regardless of whether they were administered QD-Apt
or QDs. In brief, the developed nanoprobe (QD-Apt) hasa great potential as a novel
fluorescence contrast agent for the molecular diagnosis, image-guided surgery, and
postoperative examination of gliomas.
Clearly, engineering more compact nanoprobes for fluorescence imaging is currently a research area of great practical interest. A key aspect in this reasearch area is
to try to enhance the final uptake of the QD-based nanoprobes in the cellular media.
To achieve this goal, much effort is directed towards avoiding (or reducing) eventual
QD aggregation or deposition in endosomes or lysosomes. In addition, studies to
162
Reprinted from the journal