Advancements in Medical Technology

in
Viral
Aubrey
Lewis , Ruchi Patel , Zach Pipkin , David Rash
and Prionic Infections
1

Biological Sciences,2Textiles

abstract

Methods & Results

Infectious agents such as viruses and prions spread through organ

systems via multiple pathways. Viruses attack the body by
replicating themselves inside of the cells of living organisms, while
prions are misfolded proteins that can result in neurological damage.
Many research efforts are dedicated to understanding these
diseases, as well as establishing new treatment methods with better
technology. While antiviral drugs and injections are effective, viral
resistance still remains an issue. With prionic diseases, treatment is
currently being focused on slowing down disease progression by
diminishing the rate of replication with the use of various chemicals.
An example of a technology that is being used to improve treatment
methods includes nanomedicine, which allows for devices to be built
at a molecular scale in order to target harmful cells. Recently,
scientists have developed silver nanoparticles containing antiviral
activity against the H1N1 influenza A virus. Researchers have also
found gold nanoparticles to show curing effects on prion-infected
cells. In addition to nanotechnology, light-emitting polymer
technology could soon replace the need for harmful chemical
treatments and surgery. In the future, scientists could possibly
implement technologies such as luminescent conjugated polymers
as anti-prion compounds. With these newer technologies, methods
currently used in treating diseases such as viruses and prions should
be greatly improved in the near future.

A chitosan solution was prepared in the lab by mixing various solutions and Ag NP
composites. The Ag NP composites were developed in various sizes in order to observe
the effect of size on Ag NPs antiviral activity. Human influenza A virus was obtained and
viral suspension was added to the Ag NP/Ch composite Antiviral activity was calcualated. 1

DISCUSSION

Antiviral activity of the Ag NP/Ch

increased with the increasing amount of
Ag NPs, though stronger antiviral activity
was generally observed from smaller
sized Ag NPs.
Chitosan treatment alone did not exhibit
antiviral activity
Overall, this suggests Ag NPs are
essential for antiviral activity of the
composites.
Gold nanoparticles were coated with oppositely charged polyelectrolytes and tested to see
if they could have any potential inhibition of prion protein aggregation effects and prevent
prion conversion
and replication in mice.2
1
2(b)

background
% survival

RML control mice

Nanogold 2A treated mice
Nanogold 5S treated mice

Viruses: Viruses are infectious agents with high mutation rates

and methods of natural selection, meaning they can evolve
and replicate very quickly, making treatment more difficult.

Polymers: Polymer science has great potential benefit for

future textile, biological, and medical applications. Polymers
are useful and interesting molecules in medicine, science,
and production due to their unique chemical and physical
properties as well as their (generally) low cost of production.

Future Work:
The biggest problem that scientists are experiencing is that when
attempting to denature prionic proteins, they also denature normal proteins
that are needed to live.
Since many individuals that are affected with prion diseases live in rural
areas, it would be difficult to provide the treatment. The treatment would
also need to be fairly inexpensive to help everyone infected with prions.

RESEARCH PROPOSAL

Fig. 1: Effect of the nanoparticles on fibril formation

and ASA lag phase compared between different
molecular devices: Graph A shows the results from
the SpectraMax M5 molecular device. Graph B
shows the results from the Gemini EM instruments.

In Graph A, 2A and 5S, used in concentrations of

50 pM and 200 pM respectively, both prolonged
the lag phase by around 515 hours, which
shows results of a much slower kinetics than the
control which is found in Graph B.
In vitro, these gold nanoparticles directly
interacted with PrP and prevented it from
converting into the pathogenic PrPSc-like form.

Scientists have found that amphiphilic copolymer polycyanocrylate

nanoparticles that are PEGylated diffuse more efficiently through the
blood-brain barrier than non-PEGylated nanoparticles. PEGylation can
provide water solubility to hydrophobic drugs and proteins.
Hypothesis
We hypothesize that PEGylated polycyanoacrylate nanoparticles may
serve as a vector for astemizole delivery in bovine models for treatment
of bovine spongiform encephalopathy.
Research Design

Days Post Challenge

Nanomedicine: Over time, nanomedicine has allowed for

scientists and researchers to developmany mechanisms
including drug delivery systems. In addition to many other
uses, large surface area ratio of the nanoparticles enable
them to add functionalities by attaching molecules such as
ligands to the surface.

Although science is still trying to solve many questions related to prionic

diseases and is currently working on understanding these diseases, the
main focus lies in targeting prion proteins without harming the normal
neural proteins.

Introduction

SURVIVAL TIME

Prions: Prions are infectious protein particles that cause

neurological disease in the brains of host organisms by
causing the misfold of healthy proteins that aggregate to form
porous legions in the brain, thereby inhibiting neural
communication. There is no cure for prion diseases but there
is much work being done with yeast cells, synthetic
chemicals, and nanoparticles.

Viral and prionic infections affect global health and developing better
understanding of these diseases as well as perfecting sciences like
nanomedicine and polymer science will shed light on improved and novel
treatment options.

Fig. 2: Survival Time: This graph describes the

survival time among the three different
treatment groups used in the experiment

In vivo, only 2A-treated animals showed a

significant increase of survival time when
compared with controls. However, treatment
with nanoparticles 5S was not as effective.

Researchers suggest that luminescent conjugated polymers (LCPs) may possess antiprion
properties. In order to test this hypothesis, mice were cerebrally inoculated with a strain of
3
A PrPC is in a reversible thermodynamic equilibrium
prion diseases and injected with LCP.Figure
with PrP*, which aggregates into amyloid fibrils PrP Sc. When
the fibrils reach a certain length, fragmentation occurs,
which allows for the newly formed ends of the fragments to
now act as sites for further fibril growth.
Figure B The antiprion activity of the LCPs seems to be
based on interactions with PrPSc aggregates, possibly
enhancing compactness. LCP coated PrPSc embed
preexisting prions and even PrPC. The higher compactness
of the PTAA treated aggregates ultimately causes less
fragmentation reducing the number of particles that can
replicate.

In our proposition, the drug astemizole is carried by a hydrophobic

polycyanocrylate particle core which is surrounded by the hydrophilic
PEG part. Astemizole was chosen as the experimental drug in this study
because it is an antihistamine drug that has been shown to cross the
blood brain barrier in order to bind with protein folds related to prion
diseases, and is a current focus of prion treatment research. We plan on
infecting three groups of female cattle (aged 12 years, similar body
weight) with Bovine Spongiform Encephalopathy (BSE). The experiment
will be conducted when the three groups are at an intermediate stage of
the disease; in other words, non-clinical symptoms will be observed.
One group of cattle will be the control group and will receive no
treatment for their BSE. The next group will receive the drug astemizole
through a non-PEGylated nanoparticle to assess how quickly the drug
works without the aid of polyethylene glycol polymer chains expediting
its cross of the blood-brain barrier. The final group will receive both the
anti-prion drug astemizole and the PEGylated nanoparticles to see how
quickly the drug works with the help of an amphiphilic copolymer
nanoparticle. The presence of the astemizole as well as whether or not
the nanoparticles are PEGylated or not represent the independent
variables. The dependent variable is the number of dense plaque fiber
buildups caused by prion protein aggregates. These will be counted in a
sample of brain tissue from each cow after it is euthanized after a time
period of six months.

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