• Dendrimers: The tiny tentacles shown to

    From ScienceDaily@1:317/3 to All on Wed Aug 11 21:30:42 2021
    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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