Chemistry Reference
In-Depth Information
PEg linkage. This kind of UCNP was applied for targeted imaging of mice bearing α
v
β
3
-overexpressing U87mg tumours.
Upconversion emission signals at 800 ± 10 nm can be collected from the position of the tumour. Comparing with the control
groups, this study demonstrated the good target effect between RgD conjugated UCNPs and integrin-containing tumours.
These tumour target imaging examples demonstrate that Ln-UCNPs are promising candidates as luminescent labels for
the cancer diagnosis and therapy.
13.4.4.7 Photo-Triggered Systems
Because NIR excitation has large penetration depth in bioissues, Ln-UCNPs were
also introduced to photo-triggered systems to manipulate the signals by NIR light. Zhao and co-workers used micelles
composed of poly(ethylene oxide)-block-poly(4,5-dimethoxy-2-nitro-benzyl methacrylate) and NaYF
4
:Yb,Tm nanopar-
ticles to demonstrate this concept [81]. Under excitation at 980 nm, the micelles dissociated to release the co-loaded
hydrophobic species. These light-responsive polymeric systems were suitable for potential biomedical applications such
as drug delivery. Liu and co-workers further developed a system for
in vitro
and
in vivo
photo-triggered bioluminescence
imaging [82]. The upconversion luminescence of NaYF
4
:Yb,Tm nanoparticles were able to trigger the release of D-luciferin
from D-luciferin-coujugated UCNPs. The bioluminescence of D-luciferin (λ = 560 nm) was then detectable after irradiation
by 980 nm laser.
13.4.5
multifunctional Imaging
In Vitro
and
In Vivo
multimodality imaging, including upconversion luminescent imaging techniques, can provide more information than single
modal imaging techniques. Benefitting from the unique optical and magnetic properties of rare earth ions, conventional
imaging techniques can be integrated to the upconversion luminescent imaging technique, employing UCNPs as the probes.
13.4.5.1 In Combination with Magnetic Resonance Imaging (MRI)
magnetic resonance imaging (mRI) is an impor-
tant conventional imaging technique in clinical practice. The relaxation of protons gives three-dimensional information in
the detected region. However, the poor spatial resolution limits the application of mRI technique. The combination of UCL
and mRI gives the possibility of collecting 3D information by mRI, followed by highly sensitive UCL imaging to draw the
outlines for the region of interest.
Because gd
3+
has seven unpaired electrons in its ground state, it has a large paramagnetic moment, which has strong
interaction with surrounding protons to generate T
1
enhancement in mRI. Thus gd
3+
-containing species are usually used as
T
1
-enhanced mR contrast agents [83]. Rare earth ions have similar ionic radii and charges; therefore, gd
3+
can be easily
introduced to the crystal lattice of Ln-UCNPs as host or doping ions. Heyon and co-workers first demonstrated the T
1
-
weighted mR images of SK-BR-3 cells with 20 nm NagdF
4
:Yb,Er nanoparticles [84]. Li and co-workers have used NagdF
4
as host materials to synthesise Ln-UCNPs. The as-prepared Ln-UCNPs have an r
1
value of 5.6 s
-1
mm
-1
together with the
intense UCL emission under CW excitation at 980 nm [47].
In vivo
upconversion and T
1
-weighted mR images confirm the
existence of UCNPs in liver and spleen. Similarly, gd
2
o
3
, [85] NagdF
4
, [86] BagdF
5
, [87] KgdF
4
, [88] and gdvo
4
[89] can
be used as host materials for UCL/mR two-modality imaging.
Because the interactions between gd
3+
and protons are affected by the distance between them, only the gd
3+
ions on the
surface of Ln-UCNPs have the chance to be coordinated by the neighbouring protons from water molecules. van veggel and
co-workers synthesised a series of NagdF
4
UCNPs with different sizes to investigate this effect [90]. The r
1
values increased
with decreasing particle size. Shi et al. found that the gd
3+
buried deep within crystal lattices, larger than 4 nm, has nearly no
T
1
-enhancement effect (Figure 13.10) [91]. According to this principle, fabrication of NaYF
4
:Yb,Er@NagdF
4
@Sio
2
with a
diameter of 26.2 nm gave the highest r
1
value of 6.18 s
-1
mm
-1
(the shell thickness of NagdF
4
is 0.2 nm).
Another approach for the introduction of gd
3+
is to use gd
3+
as a co-dopant as well as activator ions. Li and co-workers
have reported gd, Yb, and Er co-doped UCNPs with gd
3+
concentrations up to 60% [92]. The r
1
value is 0.41 s
-1
mm
-1
for
these kinds of materials, which is significantly smaller than those using gd-based materials as host because of the relatively
low concentration of gd
3+
. Shi and co-workers also prepared NaYF
4
:Yb,Tm,gd@mSio
2
for
in vivo
mRI and UCL imaging
with injection of probes into the tumour issues directly [93]. Several materials, such as NaYF
4
:gd,Yb,Er, [94]
NaLuF
4
:gd,Yb,Tm, [95] and BaF
2
:Yb,Tm@SrF
2
:Nd,gd, [96] are synthesised to perform similar experiments.
T
2
-enhancement mRI imaging is usually obtained with the assistance of Fe
3
o
4
nanoprobes. Due to the similarities bet-
ween Fe
3
o
4
and Ln-UCNPs, probes for the combination of UCL and T
2
-enhanced mRI imaging are often constructed by the
fabrication of heterostructures composed of Ln-UCNPs and magnetic iron oxides. Shi and co-workers fabricated such a
heterostructure via a 'neck-formation' strategy [97]. Silica shells are formed outside Fe
3
o
4
and Ln-UCNPs, respectively, in
the initial stage of the reaction. The growth of the silica shell will link two or more silica-coated NPs together to form hetero-
structures with random amounts of both Fe
3
o
4
and Ln-UCNPs. T
2
-weighted mR and UCL imaging of tumours in small
animals was demonstrated by intra-tumour injection with such heterostructures.
