1 3
Topics in Current Chemistry (2020) 378:35
fluorescence imaging. Selective detection of multiple tumor biomarkers, monitoring of molecular surface dynamics of membrane-associated molecules, measurement of cell motility or quantification of molecular interactions at the cellular and subcellular levels through fluorescent imaging are just some examples
of the growing importance of this field [140]. More specifically, the prominent
relevance of cancer research in the life sciences has promoted studies on the location and distribution of tumors and tumour cells using fluorescent in vivo imaging. To obtain an insight in the trafficking of cancer cells, such cells are labeled
with QDs that have been surface modified with antibodies. As an example, in one
study QDs were encapsulated in carboxylated triblock polymeric micelles and
conjugated with anti-mesothelin antibodies to allow targeting of the cancerous
areas [143]. An in vivo imaging study demonstrated that the QD-loaded nanomicelles, surface modified with the antibodies, targeted the pancreatic tumor site in
only 15 min after intravenous injection, thereby illustrating the potential of these
structures as promising nanoscale platforms for early human pancreatic cancer
detection.
The first challenge when designing imaging contrast agents based on QDs is to
successfully deliver the nanoplatform into the cell. Cellular penetration of QDs can
be achieved using different approaches based on both active and passive transportation. The major transport pathway of QDs into cells is endocytosis, a process in
which eukaryotic cells ingest a part of their plasma membrane to swallow external
objects. Passive transduction of QDs into the cell is mostly enabled via electrostatic
interaction with the plasma membrane. This is the most likely mechanism in the
case of water-stabilized QDs without functionalization with BMs. However, in this
latter scenario there is no guarantee of efficient uptake.
It must be mentioned that to date the mechanisms of cellular uptake and cytotoxicity of NPs are still largely understood. Some studies have demonstrated that
cellular uptake pathways are strongly dependent on cell type and cell differentiation
(e.g. monocytes showed cellular uptake of QDs surface modified with carboxylic
acid, while lymphocytes did not) [144]. Other studies have demonstrated that QD
coatings highly affect their cellular uptake. As an example, the surface modification of QDs with PEG was found to block non-specific QD delivery into the cells,
while QDs coated with carboxyl or amine groups could be internalized quickly and
at large amounts by different types of cells [145]. Thus, it is difficult to provide a
general statement on the mechanisms for cellular uptake of QDs. The results of a
study by Xiao et al. [145] suggest a potential pathway for QD cellular uptake mechanism consisting of three main stages. The first is endocytosis, which may occur
through two major mechanisms: phagocytosis and pinocytosis. In the case of small
QDs it is envisaged that endocytosis happens via micropinocytosis (a subcategory of
pinocytosis that is preferred for the uptake of smaller particles through the formation
of endocytic vesicles of different sizes). The second stage is sequestering in early
endosomes, and the third stage is translocation to later endosomes or lysosomes.
Xiao et al. found that endocytosis was probably assisted by receptors specific to
ligands with negative charges [145]. All of these findings are of great relevance to
improve the specific targeting of QDs in bioanalytical and medical applications as
they are related to reducing non-specific targeting.
161
Reprinted from the journal
Topics in Current Chemistry (2020) 378:35
fluorescence imaging. Selective detection of multiple tumor biomarkers, monitoring of molecular surface dynamics of membrane-associated molecules, measurement of cell motility or quantification of molecular interactions at the cellular and subcellular levels through fluorescent imaging are just some examples
of the growing importance of this field [140]. More specifically, the prominent
relevance of cancer research in the life sciences has promoted studies on the location and distribution of tumors and tumour cells using fluorescent in vivo imaging. To obtain an insight in the trafficking of cancer cells, such cells are labeled
with QDs that have been surface modified with antibodies. As an example, in one
study QDs were encapsulated in carboxylated triblock polymeric micelles and
conjugated with anti-mesothelin antibodies to allow targeting of the cancerous
areas [143]. An in vivo imaging study demonstrated that the QD-loaded nanomicelles, surface modified with the antibodies, targeted the pancreatic tumor site in
only 15 min after intravenous injection, thereby illustrating the potential of these
structures as promising nanoscale platforms for early human pancreatic cancer
detection.
The first challenge when designing imaging contrast agents based on QDs is to
successfully deliver the nanoplatform into the cell. Cellular penetration of QDs can
be achieved using different approaches based on both active and passive transportation. The major transport pathway of QDs into cells is endocytosis, a process in
which eukaryotic cells ingest a part of their plasma membrane to swallow external
objects. Passive transduction of QDs into the cell is mostly enabled via electrostatic
interaction with the plasma membrane. This is the most likely mechanism in the
case of water-stabilized QDs without functionalization with BMs. However, in this
latter scenario there is no guarantee of efficient uptake.
It must be mentioned that to date the mechanisms of cellular uptake and cytotoxicity of NPs are still largely understood. Some studies have demonstrated that
cellular uptake pathways are strongly dependent on cell type and cell differentiation
(e.g. monocytes showed cellular uptake of QDs surface modified with carboxylic
acid, while lymphocytes did not) [144]. Other studies have demonstrated that QD
coatings highly affect their cellular uptake. As an example, the surface modification of QDs with PEG was found to block non-specific QD delivery into the cells,
while QDs coated with carboxyl or amine groups could be internalized quickly and
at large amounts by different types of cells [145]. Thus, it is difficult to provide a
general statement on the mechanisms for cellular uptake of QDs. The results of a
study by Xiao et al. [145] suggest a potential pathway for QD cellular uptake mechanism consisting of three main stages. The first is endocytosis, which may occur
through two major mechanisms: phagocytosis and pinocytosis. In the case of small
QDs it is envisaged that endocytosis happens via micropinocytosis (a subcategory of
pinocytosis that is preferred for the uptake of smaller particles through the formation
of endocytic vesicles of different sizes). The second stage is sequestering in early
endosomes, and the third stage is translocation to later endosomes or lysosomes.
Xiao et al. found that endocytosis was probably assisted by receptors specific to
ligands with negative charges [145]. All of these findings are of great relevance to
improve the specific targeting of QDs in bioanalytical and medical applications as
they are related to reducing non-specific targeting.
161
Reprinted from the journal