Nanodiscs made of erythrocyte membranes neutralize bacterial toxins
Tiny, disc-shaped pieces of membrane called nanodiscs offer
exciting possibilities for nanomedicine. Although they have previously
been mostly made of synthetic lipids and proteins, a research team has
now introduced nanodiscs based on the cell membranes of human red blood
cells. As reported in the journal Angewandte Chemie, they are
able to neutralize dangerous bacterial toxins.
© Wiley-VCH, re-use with credit to ‘Angewandte Chemie’ and a link to the original article.
Nanodiscs are disc-shaped lipid bilayers with diameters
mostly under 20 nm. They are surrounded and stabilized by scaffolds made
of proteins, peptides, or synthetic polymers. Because of their disc
shape, they are significantly less likely than their spherical
counterparts to be “swallowed” and destroyed by immune cells. They are
thus attractive for applications like targeted drug transport. Their
small size and disc shape allows nanodiscs to effectively enter lymph
nodes, making them potentially useful as nanovaccines.
Previous nanodiscs have primarily been based on synthetic
lipid bilayers whose lipid compositions must be carefully-and
laboriously-optimized for specific applications. In addition, synthetic
lipids can trigger undesirable immune reactions. A team led by Liangfang
Zhang at the University of California, San Diego (La Jolla, USA) are
using natural cell membranes as starting materials for nanodiscs.
Natural membranes contain native lipids and proteins whose biological
functions are maintained in the nanodiscs, which could be
therapeutically useful. The team demonstrated their concept with
membranes from red blood cells.
Red blood cells were made to burst, and their membranes
were separated out and mixed with a copolymer of styrene and maleic
acid. This resulted in the formation of nanodiscs (NDs) consisting of
the natural membrane lipids and proteins from the red blood cells (RBCs)
and stabilized by the copolymer. Called RBC-NDs, these tiny structures
can be stored for long periods and are both biocompatible and non-toxic.
Interestingly, these RBC-NDs are capable of effectively
neutralizing certain bacterial toxins, as demonstrated in tests with
α-toxin from a strain of methicillin-resistant Staphylococcus
aureus. S. aureus is found almost everywhere and is usually
harmless. However, in immunocompromised patients, open wounds, or after
operations, for example, it can spread and cause life-threatening lung
infections, toxic shock, and sepsis. Strains that are resistant to
antibiotics are particularly dangerous. The primary toxin from these
bacteria, α-toxin, destroys blood cells (hemolysis). In vitro,
RBC-NDs can bind α-toxin and neutralize its hemolysis and cytotoxicity. In
vivo, injection of RBC-NDs significantly improved the chances of
survival in mice that had been given α-toxin or a complex mixture of the
various proteins excreted by S. aureus.
The design strategy used for the RBC-NDs could also be
extended to other types of membranes for a wide range of applications.
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About the Author
Dr. Liangfang Zhang is the Joan and Irwin Jacobs Chancellor
Professor of Nanoengineering and Bioengineering at the University of
California San Diego. His main specialty is biomimetic nanotechnology
with a particular focus on biomimetic nanodelivery and biological
neutralization.
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