Bioactive nano-capsules to hijack cell behavior

Date:
September 14, 2020
Source:
University of Basel
Summary:
Many diseases are caused by defects in signaling pathways of
body cells.

In the future, bioactive nanocapsules could become a valuable tool
for medicine to control these pathways. Researchers have taken an
important step in this direction: They succeed in having several
different nanocapsules work in tandem to amplify a natural signaling
cascade and influence cell behavior.



FULL STORY ==========================================================================
Many diseases are caused by defects in signaling pathways of body
cells. In the future, bioactive nanocapsules could become a valuable tool
for medicine to control these pathways. Researchers from the University
of Basel have taken an important step in this direction: They succeed
in having several different nanocapsules work in tandem to amplify a
natural signaling cascade and influence cell behavior.


========================================================================== Cells constantly communicate with each other and have ways to pick up
signals and process them -- similar to humans who need ears to hear
sounds and knowledge of language to process their meaning. Controlling
the cell's own signaling pathways is of great interest for medicine in
order to treat various diseases.

A research team of the Department of Chemistry at the University of
Basel and the NCCR Molecular Systems Engineering develops bioactive
materials that could be suitable for this purpose. To achieve this,
the researchers led by Professor Cornelia Palivan combine nanomaterials
with natural molecules and cells.

In the journal ACS Nano, they now report how enzyme loaded
nano-capsules can enter cells and be integrated into their native
signaling processes. By functionally coupling several nano-capsules,
they are able to amplify a natural signaling pathway.

Protecting the cargo In order to protect the enzymes from degradation
in a cellular environment the research team loaded them into polymeric
small capsules. Molecules can enter the compartment through biological
pores specifically inserted in its synthetic wall and react with the
enzymes inside.



==========================================================================
The researchers conducted experiments with nano-capsules harboring
different enzymes that worked in tandem: the product of the first
enzymatic reaction entered a second capsule and started the second
reaction inside. These nano- capsuled could stay operative for days and actively participated in natural reactions in mammalian cells.

Tiny loudspeakers and ears One of the many signals that cells receive
and process is nitric oxide (NO). It is a well-studied cellular mechanism
since defects in the NO signaling pathway are involved in the emergence of cardiovascular diseases, but also in muscular and retinal dystrophies. The pathway encompasses the production of NO by an enzyme family called
nitric oxide synthases (NOS). The NO can then diffuse to other cells
where it is sensed by another enzyme named soluble guanylate cyclase
(sGC). The activation of sGC starts a cascade reaction, regulating a
plethora of different processes such as smooth muscle relaxation and
the processing of light by sensory cells, among others.

The researchers lead by Palivan produced capsules harboring NOS and sGC,
which are naturally present in cells, but at much lower concentrations:
the NOS- capsules, producing NO, act similarly to loudspeakers, "shouting" their signal loud and clear; the sGC-capsules, act as "ears," sensing
and processing the signal to amplify the response.

Using the intracellular concentration of calcium, which depends on the
action of sGC, as an indicator, the scientists showed that the combination
of both NOS and sGC loaded capsules makes the cells much more reactive,
with an 8-fold increase in the intracellular calcium level.

A new strategy for enzyme replacement therapy "It's a new strategy to
stimulate such changes in cellular physiology by combining nanoscience
with biomolecules," comments Dr. Andrea Belluati, the first author of
the study. "We just had to incubate our enzyme-loaded capsules with the
cells, and they were ready to act at a moment's notice." "This proof
of concept is an important step in the field of enzyme replacement
therapy for diseases where biochemical pathways malfunction, such as cardiovascular diseases or several dystrophies," adds Cornelia Palivan.


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


========================================================================== Journal Reference:
1. Andrea Belluati, Ioana Craciun, Cornelia G. Palivan. Bioactive
Catalytic
Nanocompartments Integrated into Cell Physiology and Their
Amplification of a Native Signaling Cascade. ACS Nano, 2020; DOI:
10.1021/ acsnano.0c05574 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200914095903.htm

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