Fluorescence image of breast cancer cells incubated with dye-loaded BSA
nanoparticles showing that the nanoparticles have entered the cell cytoplasms
(red) but not the nuclei (blue)
Fluorescent dyes with aggregation-induced emission provide new probes
for cancer diagnosis and therapy
Fluorescent nanoparticles loaded
with organic light-emitting dyes are expected to transform live-animal imaging
technologies. Compared to inorganic quantum dots, these optically stable
materials are non-toxic and can easily be modified with functional groups,
making them ideal when targeting specific tissues in the body. Unfortunately,
traditional dyes have been known to aggregate and lose their emission intensity
when incorporated in nanoparticles at high concentration. To overcome this
problem, a team of researchers led by Bin Liu and Ben Zhong Tang at the A*STAR
Institute of Materials Research and Engineering have now designed a family of
dyes with enhanced fluorescence upon aggregation1.
At the heart of the traditional
dyes is a planar chromophore called triphenylamine-modified dicyanomethylene,
which emits red light in dilute solutions but fluoresces weakly when
aggregated. “The close vicinity of the chromophores induces fluorescence quenching
due to non-radiative pathways,” says Liu.
Liu, Tang and their team reversed
this phenomenon by attaching propeller-shaped tetraphenylethene pendants to
each extremity of the chromophore. Contrary to planar compounds, the shape of
the propellers prevents strong stacking interactions between chromophores,
blocking the aggregation-caused quenching process. In addition, the physical
confinement prevents these propellers from rotating freely, enabling light
emission.
The team formulated the dyes
using a bovine serum albumin (BSA) matrix — a biocompatible and clinically used
polymer — and evaluated their performance as probes. Experimental
characterization showed that the wavelength of the emission maximum of the
nanoparticles remained unchanged upon encapsulation and that the intensity of
the emitted light increased with the dye loading.
Live imaging of breast cancer
cells revealed that the nanoparticles displayed more intense and homogeneously
distributed red fluorescence in the cytoplasms (see image) than free
aggregates, suggesting that BSA boosted the cellular uptake of the dyes. The
team also found that the nanoparticles were optically stable in biological
media and displayed good biocompatibility.
The researchers intravenously
injected the nanoparticles in liver-tumor-bearing mice for in vivo imaging
studies. They found that unlike free aggregates, the nanoparticles selectively
accumulated in the tumor, clearly highlighting the cancerous tissue in the
animals. “This demonstration underscores new research opportunities to explore
similar diagnostic probes with potential clinical applications,” says Liu.
The team is currently
investigating near-infrared emissive biological probes for targeted in vivo
tumor imaging applications. The nanoparticles can also be utilized to
understand cancer metastasis or the fate of transplanted stem cells. “These
probes are promising in multimodal imaging applications through integration
with magnetic resonance imaging or nuclear imaging reagents,” says Liu.
The A*STAR-affiliated researchers
contributing to this research are from the Institute of Materials Research and
Engineering
References
- Qin, W. et al. Biocompatible
nanoparticles with aggregation-induced emission characteristics as
far-red/near-infrared fluorescent bioprobes for in vitro and in
vivo imaging applications. Advanced Functional Materials 22,
771–779 (2012). | article
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