Illuminating the brain | SEHS-China

Bioluminescence

Bioluminescence is a fascinating
natural phenomenon that emits
visible light through a chemical
reaction within living organisms
such as bacteria, marine
organisms, and insects [1-3].

Firefly Bioluminescence

The North American firefly
(Photinus pyralis) is a predominant
bioluminescent species among
insects. Such a firefly
luciferin-luciferase bioluminescent
system has been well studied for at
least 50 years [4, 5].

Firefly luciferin-luciferase
Reaction

In the firefly
luciferin-luciferase system,
luciferase functions as an
enzyme while luciferin serves
as a substrate [5]

Would it be possible to
employ this system in the
field of oncology to
illuminate our brains?

Brain Tumors

Brain is one of the most important
organs of human beings, no matter
whether the tumor in the brain is
benign or malignant, once it
compresses any part of the brain, it
will affect the health of human body.

The Harmfulness of
the Brain Tumor

Intracranial tumors, making up a
significant percentage of overall and
childhood tumors, can
raise intracranial pressure and
cause central nervous damage,
threatening the patient's life [6, 7].

Treatment for Brain Tumor

Surgical removal of the tumor is
the most effective therapy for
brain tumors. The majority of
malignant brain tumors are not
entirely surgically removed and
will recur. Consequently, taking
advantage of a tracer to monitor
the tumor is a critical component
of patient treatment [8].

Application of luciferase
substrates are restricted
by the following:

Limited red-light emission, short in vivo
duration and low blood-brain barrier
permeability.

Our Project

This project aims to develop cyclic N-aminoluciferins
(cyL) with enhanced bioluminescence properties as novel
firefly luciferase substrates after rational design.

We used various cycloaminobenzothiazol-2-nitriles as
starting materials to prepare four novel cyL compounds
following a cyclization with D-cysteine in the presence
of potassium carbonate.

We subsequently conducted a series
of bioluminescence assays and
imaging studies to test if cyL
compounds can address those issues
like short red-light emission, short
bioluminescence duration, and low
blood-brain barrier permeability.

Consequently, these modified
luciferase substrates have the
potential to improve their properties
and reshape living animal imaging,
particularly for the purpose of
monitoring brain tumor progression
and looking for therapies.

EXPLORE MORE

References

1. Herring, P. J. Bioluminescence of marine organisms. Nature, 1977, 267, 788-793.
2. Dothager, R. S.; Flentie, K.; Moss, B.; Pan, M.-H.; Kesarwala, A.; Piwnica-Worms, D. Advances in
bioluminescence imaging of live animal models. Current Opinion in Biotechnology, 2009, 20, 45-53.
3. Widder, E. A. Bioluminescence in the Ocean: Origins of Biological, Chemical, and Ecological Diversity. Science,
2010, 328, 704-708.
4. Maggi, A.; Ciana, P. Reporter mice and drug discovery and development. Nat Rev Drug Discov, 2005, 4,
249-255.
5. Li, J.; Chen, L.; Du, L.; Li, M. Cage the firefly luciferin! - a strategy for developing bioluminescent probes.
Chem Soc Rev, 2013, 42, 662-676.
6. van den Bent, M. J.; Geurts, M.; French, P. J.; Smits, M.; Capper, D.; Bromberg, J. E. C.; Chang, S. M.
Primary brain tumours in adults. Lancet, 2023, 402, 1564-1579.
7. Igoshina, E.; Wu, L. C.; Moxon-Emre, I.; Mabbott, D. J. Social affective outcomes and brain injury in
children and adolescents treated for brain tumours. Lancet Child Adolesc Health, 2023, 7, 577-587.
8. Tan, A. C.; Ashley, D. M.; Lopez, G. Y.; Malinzak, M.; Friedman, H. S.; Khasraw, M. Management of
glioblastoma: State of the art and future directions. CA Cancer J Clin, 2020, 70, 299-312.