A new fluorescent glucose-amine probe can make identification of cancer
cells (green) using two-photon microscopy easier and safer.
Glucose–amine rings turn star-shaped fluorescent dyes into powerful
probes for imaging cancer cells in three dimensions
Early detection of soft-tissue
diseases, such as breast cancer, typically requires invasive biopsies. Now, a
new self-assembled nanoparticle developed by Bin Liu at the A*STAR Institute of
Materials Research and Engineering and co-workers1 may soon make biopsies
obsolete. The team’s material significantly enhances the safety of two-photon
microscopy (TPM) — a technique that uses fluorescent probes to generate
three-dimensional pictures of cancer cell structures in living tissue.
Although TPM provides deep access
to cell tissue without significant photo-damage, finding suitable substances to
act as light-emitting probes is challenging. ‘Quantum
dots’made from nanoscale aggregates of
elements such as cadmium and selenium are excellent cell-structure
illuminators, thanks to their bright and stable fluorescence. However, their
inherent toxicity restricts many possible biological applications.
Liu and her team therefore turned
to conjugated organic molecules to produce less toxic dyes for TPM. While such
small organic molecules are normally unable to absorb sufficient amounts of
laser light to initiate fluorescence imaging, the team resolved this problem by
synthesizing a star-shaped material known as a dendrimer. Consisting of a
central triphenyl amine core and three ‘arms’ made from extended conjugated
chains, this unique geometry can induce much larger cross sections that can
absorb two-photons better than isolated fluorescent dyes.
To ensure biocompatibility
between the star-shaped dendrimer and cell tissue, the researchers had to
employ a chemical trick. Inspired by the versatile binding behavior of
chitosan, a natural polysaccharide, the team used a mild bromide–thiol reaction
to attach several glucose–amine sugar rings to the dendrimer’s arms. According
to Liu, this process lowered the cytotoxicity of the dye and enabled them to
functionalize it with folic acid ligands that target the surfaces of a breast
cancer cell line known as MCF-7.
The team’s experiments showed
that the dendritic dye self-assembled into dispersed nanoparticles when
submerged in water — a form that increases two-photon-absorption cross sections
and provides a high yield of laser-induced fluorescence. When they incubated
these nanoparticles into the MCF-7 cells, subsequent TPM imaging revealed a
bright fluorescence localized inside the cancer cell cytoplasma (see image).
This data indicates that specific binding occurs between the dendritic dye and
folate receptors on the MCF-7 surface.
Cell viabilities close to 100% at
dye concentrations used for imaging studies confirms that this strategy is a
safe and promising way to increase the use of TPM imaging. “We are keen to
expand the current in vitro imaging to in vivo applications,” notes Liu.
The A*STAR-affiliated researchers
contributing to this research are from the Institute of Materials Research and
Engineering
References
- Wang, G., Zhang, X., Geng, J., Li, K., Ding, D. et
al. Glycosylated star-shaped conjugated oligomers for targeted
two-photon fluorescence imaging. Chemistry – A European Journal 18, 9705–9713
(2012). | article
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