Chemistry Reference
In-Depth Information
probe with higher quantum efficiency, Li and co-workers reported the imaging with penetration depth larger than 1.5 cm in
a mouse [4] or packing pork [60].
13.4.2.4 High Sensitivity
Due to the rapid development in electro-optical devices, modern instruments can collect
weak luminescent signals from minute amounts of samples. These techniques endow the luminescent imaging techniques
with high sensitivity. Cohen and co-workers reported cell imaging stained with individual NaYF
4
:Yb,Er nanocrystals with
no measurable background signals and blinking [61]. This experiment proved that the sensitivity of the upconversion
imaging technique can reach the single particle level in cell imaging. Recently, Li and co-workers tested the imaging
sensitivity in animals [4]. KB cells stained by NaLuF
4
:Yb,Tm UCNPs were injected into athymic nude mice to test the
sensitivity. After subcutaneous injection of 50 KB cells, upconversion signals were detected with a signal-to-noise ratio of
about 5. With vein injection of 1000 cells, upconversion signals can be collected in the region corresponding to the lung
of the mice.
13.4.3
ucnPs for
In Vitro
bioimaging
13.4.3.1 UCnPs for Living Cells Imaging
UCNPs with various surface modifications have been successfully used in
living cell imaging. For example, Zhang and co-workers incubated skeletal myoblasts and bone marrow-derived mesen-
chymal stem cells with silica-coated Ln-UCNPs [57]. The UCL signals were collected in the confocal images, and Ln-UCNPs
were mainly located in the cell cytoplasm. Li and co-workers also demonstrated that azelaic acid-coated Ln-UCNPs can be
used for cell imaging via the endocytosis mechanism [2]. Ln-UCNPs coated by polymers can also be used for cell imaging.
PEg, PEI, PAA, and PvP are the most commonly used polymers for the surface modification of Ln-UCNPs. van veggel's
group [62] and Li's group [63] employed PEg-based polymer-coated Ln-UCNPs to successfully image ovarian cancer cells,
respectively, whilst Capobianco and co-workers used PEI-coated Ln-UCNP to image living HeLa cells [64].
In addition, different surface properties will affect the cell uptake of Ln-UCNPs. Wong and co-workers studied the uptake
of various charged Ln-UCNPs by mammalian cells [65]. PvP (neutral), PEI (positive), and PAA (negative)-coated Ln-UCNPs
were used as models with different kinds of charges. As shown in confocal imaging and ICP-mS analysis, positively charged
PEI-coated Ln-UCNPs can be internalised by the cells more easily than the neutral or negatively charged ones.
13.4.3.2 Tumour Cell Targeting
Tumour cell targeting is important in the detection of tumour cells and the labelling of
cells for cell tracking. Some typical targeting species, such as folic acid (FA), peptides, and antibodies, have been used to
link to the Ln-UCNPs for tumour cell targeting. Folic acid is one of the most commonly used functional molecules for
tumour targeting because folate receptors (FR) are overexpressed in many human cancerous cells. Thus, FA-modified species
have high affinity to these cells.
Zhang and co-workers were the first to conjugate FA molecules to the PEI-coated Ln-UCNPs [66]. These nanoparticles
can target FR-positive human HT29 adenocarcinoma and human ovCAR3 ovarian carcinoma cell lines for upconversion
imaging. Similarly, Li and co-workers have conjugated FA molecules on the surface of Ln-UCNPs@Sio
2
[67]. The carboxyl
groups of FA are used to link with -NH
2
groups from the existing capping ligand (e.g., 6-aminohexanoic acid), activated by
sulfo-NHS and EDC. As confirmed by confocal images and quantitative flow cytometric analysis, FA-labelled Ln-UCNPs
were proven to have high efficiency to target tumour cells.
RgD peptide is another popular species for tumour targeting, based on its high affinity to the α
v
β
3
integrin receptor [68]. Li
and co-workers developed a method to label Ln-UCNPs with RgD peptide by PEg linkage, for targeted imaging of tumours
in vitro
and
in vivo
[3]. Zako and co-workers have also reported RgD labelled Y
2
o
3
:Er for U87mg cells targeted imaging [69].
The interactions between antibody and antigen comprise another way to target tumour cells. Xu and co-workers applied
anti-Her2 antibodies attached to the NaYF
4
:Yb/Er@Sio
2
nanoparticles to target Her2 receptors of SK-BR-3 cells [70].
Similar strategies have been successfully applied for the corresponding tumour cell targeting imaging with Ln-UCNPs,
using anti-claudin-4 [71], anti-mesothelin [71], or rabbit CEA8 antibody [72] as antibody, respectively.
13.4.4
ucnPs for
In Vivo
bioimaging
The upconversion imaging technique has also been demonstrated at the animal level. various kinds of animals, such as
C. elegans
, mouse, and rabbit have been employed as sample animals to evaluate their imaging qualities.
13.4.4.1 nematode
c. elegans
Imaging
Ln-UCNPs can be introduced to label
C. elegans
by simple incubation,
because
C. elegans
can eat Ln-UCNPs in the substrate. Thus the upconversion signals can be collected from inside
C.
elegans
. Lim and co-workers first reported the
in vivo
upconversion imaging of
C. elegans
fed 150 nm Ln-UCNPs [73].
