Singlet oxygen battery for photodynamic treatment of deep infections
In antibacterial photodynamic therapy, irradiation is used
to produce reactive oxygen species that kill off bacteria. Because it
requires external light and oxygen, this method is only suitable for
surface infections. In the journal Angewandte Chemie, a Chinese
research team has now introduced a molecular “singlet oxygen battery”
that can be “charged” with reactive oxygen, which it then releases in
deep tissue layers to target methicillin-resistant staphylococcus.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Antibiotic-resistant bacteria are on the rise. Though often
harmless to healthy people, dreaded multidrug-resistant “hospital
pathogens” such as methicillin-resistant Staphylococcus aureus
(MRSA) use injuries or fresh surgical wounds to gain entry to the body.
They also infect immunocompromised patients. Because antibiotics are not
effective, there is sometimes no remedy.
One highly promising alternative is antibacterial
photodynamic therapy, which is already widely used in dentistry. In this
technique, a light-activated substance (photosensitizer) is irradiated,
triggering a photodynamic reaction that produces singlet oxygen (1O2),
an excited form of oxygen. Unlike antibiotics, this substance
simultaneously attacks multiple biomolecular sites on the bacteria. It
is easy to use, safe, painless, and generally free of side effects.
Unfortunately, it has only been useful for surface infections because
the necessary light only penetrates a few millimeters into the tissue.
Additionally deeper tissue layers also do not have enough oxygen for
effective treatment.
A team led by Bingran Yu and Fu-Jian Xu at Beijing
University of Chemical Technology has now developed a new approach to
photodynamic therapy: a “singlet oxygen battery” that can be used to
fight deep bacterial infections because it requires neither light nor
external oxygen.
The conversion of oxygen into reactive singlet oxygen
through irradiation in the presence of a molecule that captures light
(photosensitizer) happens first. The “battery” is “charged” with the
singlet oxygen. This “battery” consists of a special
nitrogen-containing, six-membered ring of carbon atoms (pyridone) that
tightly binds the singlet oxygen. The reactive oxygen molecule bridges
two opposite vertices of the ring (endoperoxide). A peptide bound to the
ring specifically “recognizes” MRSA bacteria, so the molecular batteries
accumulate around and in the bacteria and continuously release their
singlet oxygen. The bacteria are thus simultaneously attacked at many
different locations, including their membrane, DNA, enzymes, and other
proteins. This makes the development of resistance virtually impossible.
When administered to mice through nebulization, the singlet oxygen
battery was shown to be very effective in treating pulmonary infections
caused by MRSA. Systemic side effects were not observed.
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About the Author
Dr Bingran Yu is a Professor at Beijing University of
Chemical Technology. He is primarily engaged in the field of biomedical
polymers and systematically studied areas such as drug/gene-controlled
release biomaterials, as well as antimicrobial and anti-infection
biomedical materials. Dr Fu-Jian Xu is a Professor at Beijing University
of Chemical Technology, the dean of the College of Materials Science and
Engineering, and the director of the Key Lab of Biomedical Materials of
Natural Macromolecules (Beijing University of Chemical Technology,
Ministry of Education). He has been working on biomedical polymers for
over 15 years.