Afterglow luminescence imaging tracks cell-based microrobots in real time
An afterglow luminescent nanoprobe opens up new
possibilities for imaging living cells. As a research team
reports in the journal Angewandte Chemie, their new “nanotorch”
can continue to luminesce for over ten days after a single excitation.
This allows the routes taken through the body by microrobots to be
tracked in real time. In addition, it can be “recharged” non-invasively
with near-infrared (NIR) light in a non-contact manner.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Macrophages are important immune cells that “eat” bacteria
as well as being involved in the disposal of cancer cells. In addition,
they can take up drugs and transport them into cells, including tumor
cells. If they take up magnetic nanoparticles, macrophages can be guided
by magnet to a target area within the body, such as a tumor. This allows
macrophage “microrobots” to reduce the side effects associated with
chemotherapy.
It would be useful to be able to track the microrobots over
time as they move through the body. Fluorescence imaging techniques have
been considered but require constant external irradiation. This causes is a high level of background noise resulting from
the autofluorescence of many biomolecules. In addition, the limited
penetration depth of the visible and UV light through tissues required into the tissue
limits the depth of detection. One alternative could be the use of
probes that can be irradiated before the procedure and produce an
afterglow. However, inorganic nanoparticles with long-lasting afterglow
harbor the risk that heavy metal ions will leak out; while organic
compounds only luminesce for a short time and cannot be repeatedly
excited.
A team from the Shenzhen Institute of Advanced Technology,
Chinese Academy of Sciences (China) collaborating with Koç University
(Turkey) has now developed a “rechargeable nanotorch”. It is made of
multiple components: nanoparticles of a precursor to a luminescent
organic molecule, photosensitizers (a hydrophobic analog of methylene
blue), and polyethylene glycol equipped with cell-penetrating peptides.
The photosensitizer absorbs NIR light and excites surrounding oxygen
molecules. This highly reactive singlet oxygen then binds to the
precursor and forms a dioxetane group, a four-membered ring made of two
oxygen and two carbon atoms. This undergoes a rearrangement that
releases the desired luminescent molecule and emits excess energy by
luminescing. After the initial irradiation, the nanotorches continue to
luminesce for ten days.
Once depleted, the nanotorches can be “remotely” recharged
and made to luminesce again by external radiation with NIR light, which
can penetrate deep into tissues – multiple times. This requires the
relative amounts of photosensitizer and luminescent molecule precursor
to be selected so that only some of the precursors are activated with
each irradiation. This allows for imaging over longer periods of time.
The China team led by Pengfei Zhang, Ping Gong and Lintao
Cai collaborated with the Turkey team with led by Safacan-Kolemen
introduced these new nanotorches into macrophage-based microrobots and
were able to follow their magnet-guided path through the bodies of mice
in real time through the luminescence signals.
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About the Author
Dr Pengfei Zhang is an Associate Professor at Shenzhen
Institute of Advanced Technology, Chinese Academy of Sciences with
analytical chemistry and bioengineering background. His main specialty
is molecular/nanoscale probes for diagnosis, imaging, tracing, and
therapy.
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