Dendrimers: The tiny tentacles shown to evade our immune response

Date:
August 11, 2021
Source:
Newcastle University
Summary:
New research demonstrates that dendrimers, tiny synthetic particles,
can avoid detection by our immune system and could be used to
develop a new system to deliver drugs into the body without
triggering a reaction.



FULL STORY ==========================================================================
Tiny synthetic particles known as dendrimers have been shown to avoid
detection by our immune system and so could be used to develop a new
system to deliver drugs into the body without triggering a reaction.


==========================================================================
The new research led by Professor Moein Moghimi, Professor of
Pharmaceutics and Nanomedicine at the School of Pharmacy, Newcastle
University, UK, in collaboration with international colleagues is
published in Nature Communications alongside an accompanying blog.

The dendrimer is a chemically-created molecule with tentacles branching
out in a highly-symmetrical structure around a central core. The research describes how dendrimer tentacles arranged incredibly closely to each
other -- less than one nanometer apart -- avoided detection by the
complement system, part of our immune system.

Our immune system is equipped with many tools to recognise and eliminate invaders. For example, our blood contains sensors belonging to a family of defence system known as the "complement system," which recognises unique patterns expressed by invaders such as bacteria and viruses. Binding
of these sensors to pathogens alarms the immune system and triggers an
immune response.

These sensors are termed "complement pattern-recognition (CPR)" molecules.

CPR can sense surface patterns that are regularly repeated so close to
each other, for instance in 2-15 nanometer ranges -- a distance, which
is at least 5000 times thinner than the thickness of a typical sheet
of paper.

The international team discovered however, that the CPR could not sense patterns repeated closer to each other, for instance, at 1 nanometer
or less.



==========================================================================
At a nanoscale level, the team grew tiny particles known as dendrimers
which are shaped like trees with many branches -- or tiny tentacles. The
number of tentacles exponentially increases with dendrimer size and the tentacles are positioned less than 1 nanometer from each other. The ends
of tentacles are where regular patterns appear. Depending on chemical
structure of these patterns, they found that these dendrimers could
escape detection by the CPR radar.

Professor Moein Moghimi explains: "This discovery shows that we can
develop certain dendrimers as very tiny carriers to smuggle drugs into the
body without triggering our immune system. Activation of the complement
system as the defence mechanisms of our immune system can sometimes result
in inflammation and may also induce anaphylactic reactions. One example
is we have seen anaphylaxis in some recipients of COVID-19 vaccines,
which uses small lipid particles and instead with dendrimers we could
avoid these adverse reactions." "Dendrimers offer us the ability to
deliver drugs to diseased sites where inflammation is a major problem
such as in conditions like atherosclerosis, cancer, macular degeneration
and rheumatoid arthritis," said Dr. Panagiotis Trohopoulos, cardiologist
and managing director of CosmoPHOS Ltd (Thessaloniki, Greece), co-author
of the paper.

"This could allow medical teams to treat these conditions without
triggering the patient's own immune system. That is why we chose
dendrimers in an ongoing therapeutic study in atherosclerosis," said
Dr. Trohopoulos.

The team suggests that since these complement-evading dendrimers are so
tiny they could also be used to camouflage surfaces of implants and many biomedical devices like cardiovascular stents, protecting them against
attack by the complement system.

The researchers also say that these findings suggest that some very
dangerous bacteria and viruses could be exploiting patterns to escape
our immune system.

For example, it might be possible that pathogens display surface patterns
with less than 1 nanometer periodicity from each other in order to escape
the complement system radar and survive inside the host.

Finally, the team also found that a special type of dendrimer (those
bearing amine groups on their tentacles) hitchhike on an immune molecule
called immunoglobulin M (IgM). "With these dendrimers the ride was
not free; jumping on IgM dented its structure and this triggered the
complement response," said Professor Moghimi.

The interdisciplinary team intends to develop the work further
examining the potential for drug delivery, vaccine design, and device bioengineering, as well as the basic understanding of microbial evasion
from our immune system.

========================================================================== Story Source: Materials provided by Newcastle_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Lin-Ping Wu, Mario Ficker, Jo/rn B. Christensen, Dmitri Simberg,
Panagiotis N. Trohopoulos, Seyed M. Moghimi. Dendrimer end-terminal
motif-dependent evasion of human complement and complement
activation through IgM hitchhiking. Nature Communications, 2021;
12 (1) DOI: 10.1038/s41467-021-24960-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210811131538.htm

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