Sugar-coated nanoparticles target macrophages, reverse pulmonary
fibrosis
Nanoparticle platform delivers a nucleotide that blocks production of scar-promoting protein

Date:
April 5, 2022
Source:
University of Illinois Chicago
Summary:
Scientists have developed a treatment for pulmonary fibrosis by
using nanoparticles coated in mannose -- a type of sugar -- to stop
a population of lung cells called macrophages that contribute to
lung tissue scarring. The cell-targeting method holds promise for
preventing this severe lung scarring disease, which can result in
life-threatening complications like shortness of breath.



FULL STORY ========================================================================== Scientists at the University of Illinois Chicago have developed a
treatment for pulmonary fibrosis by using nanoparticles coated in
mannose -- a type of sugar -- to stop a population of lung cells called macrophages that contribute to lung tissue scarring. The cell-targeting
method holds promise for preventing this severe lung scarring disease,
which can result in life-threatening complications like shortness of breath. 

==========================================================================
The researchers say that the treatment is not yet ready to be tested in clinical trials, but its success in relevant animal models is a promising
sign that it may be possible to treat the disease -- for which there are
very limited and imprecise treatments available.  A major cause
of lung fibrosis is the activation of harmful immune cells that cause
excessive inflammation.

"The body's inflammatory processes are very complex and finding treatments
for diseases that result from lingering or excessive inflammation are
very difficult because the treatments that prevent harmful inflammation
also, unfortunately, prevent helpful inflammation which fights infections
and heals injuries," said Abhalaxmi Singh, visiting research assistant professor in the department of pharmacology and regenerative medicine
at the UIC College of Medicine. "To have a targeted treatment that
addressed a root cause of harmful inflammation work in an animal model
is exciting."  The coated nanoparticle treatment stops fibrosis by binding to a subset of macrophages, a type of white blood cell found in
all organs, that have a receptor for mannose, a sugar molecule. This receptor, called CD206, is hyper-expressed in patients with pulmonary
fibrosis.

The scientists found that the macrophages that cause lung fibrosis
have very high levels of mannose. In pulmonary fibrosis, macrophages go
through a transition that releases cytokines and promotes scarring. Singh
and her colleagues characterized the surfaces of these scar-promoting macrophages and the CD206 mannose receptor and designed a nano-vehicle
to target these receptors.  When the sugar-coated nanoparticle
binds to the cell's receptor, it delivers the nucleotide -- a fragment of silencing RNA (siRNA) targeting transforming growth factor beta (TGFB)
-- which the researchers loaded into the nanoparticle. SiRNA targeting
TGFB is a cell signaling pathway known to be involved with pulmonary
fibrosis. Once in the cell, the nucleotide blocks the macrophage's ability
to make excessive amounts of proteins, such as collagen, involved with
scar formation.  "Macrophages are exciting, complex cells and the approach Dr. Singh and our team took in coating the nanoparticle with
sugar to bind to the mannose receptor is an intriguing and precise way
to ensure targeted delivery of a silencing RNA treatment to this subset
of cells that contribute to fibrosis," said Asrar Malik, Schweppe Family Distinguished Professor and head of the department of pharmacology and regenerative medicine.  The team has already started testing the treatment in human lung tissue samples with colleagues at the University
of California at San Francisco.  The nanoparticle used in the
experiments is formulated from a protein called albumin, and it is a
platform the scientists are studying as a tool to deliver therapeutics
for a variety of conditions.  Malik's team first discovered
that albumin nanoparticles can be used to suppress inflammation in
a precision medicine manner. Their original discovery was reported
in a 2014 Nature Nanotechnology research article. The inventors subsequently established Nano Biotherapeutics, an independent startup
company supported by a National Institutes of Health phase II Small
Business Technology Transfer grant to attract the partners and investors
needed to bring the innovation to market.


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


========================================================================== Journal Reference:
1. Abhalaxmi Singh, Sreeparna Chakraborty, Sing Wan Wong, Nicole
A. Hefner,
Andrew Stuart, Abdul S. Qadir, Amitabha Mukhopadhyay, Kurt
Bachmaier, Jae-Won Shin, Jalees Rehman, Asrar B. Malik. Nanoparticle
targeting of de novo profibrotic macrophages mitigates lung
fibrosis. Proceedings of the National Academy of Sciences, 2022;
119 (15) DOI: 10.1073/pnas.2121098119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220405143534.htm

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