Tiny peptide particles that could be used to treat bacterial and fungal infections
of the brain, such as meningitis and encephalitis, have been designed, constructed
and tested successfully by researchers led by Yi-Yan Yang from the Institute
of Bioengineering and Nanotechnology (IBN) of A*STAR, Singapore*. The nanoparticles,
which assemble themselves in water, are potent against multi-drug-resistant
bacteria and can also cross the blood–brain barrier. These custom-designed
nanoparticles have particular relevance to treating infections in people with
suppressed immune systems, such as HIV and cancer patients, the researchers
say.
 | | Schematic illustration showing how positively charged peptide nanoparticles (green) interact with and disrupt negatively charged bacterial walls. Reproduced with permission NPG Asia Materials. |
All multicellular organisms possess a variety of antimicrobial compounds known
as cationic peptides. These are chains of between 12 and 50 amino acids that
contain both water-interacting hydrophilic and fat-interacting hydrophobic regions.
Cationic peptides can insert themselves into membranes, and are particularly
attracted to negatively charged microbial membranes that they disrupt (Fig.
1), often inducing the death of the organism. Recently there has been much interest
in developing these compounds as antibiotics, because they do not easily induce
resistance in microbes.
The researchers designed their own cationic peptide from three elements—hydrophobic
cholesterol, a cell-penetrating hydrophilic peptide known as TAT, and amino
acids to separate them and add positive charge. In water, this compound self-assembles
into tiny globular nanoparticles called micelles. Less than 200 nm in diameter,
these micelles have a cholesterol core and a TAT coat.
Yang and her team at IBN determined the physical and chemical properties of
their micelles and tested the antimicrobial capabilities of the nanoparticles.
They found that their nanoparticles inhibited the growth of a wide variety of
bacteria, fungi and yeasts; but, unlike many other antimicrobials, they did
not tend to break up red blood cells.
The IBN team then collaborated with researchers at Zhejiang University in Hangzhou,
China, to test the nanoparticles in living organisms. The results showed that
the nanoparticles were effective against Staphylococcus aureus infections in
mice, and were able to cross the blood–brain barrier to suppress bacterial
growth in the brains of rabbits susceptible to meningitis. The major organs
of the test animals appeared unaffected by the treatment.
“We are now planning to conduct extensive preclinical trials to evaluate
the efficacy and toxicity of our nanoparticles,” says Yang. “We
then look forward to progressing to clinical trials over several years.”
The A*STAR affiliated authors on this highlight are from the Institute of Bioengineering
and Nanotechnology.
* Liu, L., Xu, K., Wang, H., Tan P. K. J., Fan, W., Venkatraman, S.S., Li,
L. & Yang, Y-Y. Self-assembled cationic peptide nanoparticles as an efficient
antimicrobial agent. Nature Nanotechnology 4, 457–462 (2009).
Posted November 4th, 2009
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