Emerging
Nanomaterials for Healthcare – An Interdisciplinary Conference at the
University of Warwick
Mathew P. Robin and Gemma-Louise
Davies
Department
of Chemistry, University of Warwick
Abstract
“Emerging
Nanomaterials for Healthcare”, a one-day conference held at the University of
Warwick on 28 November 2014, brought together over 80 academics, postgraduates
and industrialists from 17 institutions and organisations from across the UK. The
aim of the meeting was to provide an interdisciplinary forum to discuss
research towards solving current problems in healthcare using “smart”
treatments based on nanomaterials. In addition to stories of success, an
emphasis was also placed on lessons learned, as well as visions for future
directions in this rapidly expanding field. Seven speakers and over twenty
poster presentations directed discussion throughout the day, while the meeting
closed with an interactive panel discussion.
Keywords: Nanoparticles, nanomedicine,
nanomaterials, healthcare, medicine
In a recent editorial for the journal
Angewandte Chemie, Younan Xia asked the question ‘Are we entering the Nano Era?’ (Xia, 2014: 12268). Specifically,
Xia was pondering whether we have reached the stage where materials fabricated
with nanometre dimensions (between one and one hundred billionths of a metre)
will begin to dominate technological advances in all areas of science. The
importance of nanomaterials to the scientific community, and the impact of the
nanotechnology that these materials enable, is a consequence of a unique set of
features possessed by matter at the nanometre scale. As Stark et al. have recently noted: ‘Valuable chemical industry products are a
result of designing a set of properties within a material. Today, industrial
development therefore considers nanoparticles as an extended toolbox containing
traditionally difficult to realize properties’ (Stark et al., 2015: 2). Despite the growing importance of nanotechnology
to the areas of catalysis, pigments and composite materials, significantly less
commercial success has so far been achieved for nanomaterials in healthcare. In
his piece, Xia frames the driving forces for interest in nanotechnology applied
to biomedical research in particular, saying ‘cells are packed with complex, functional structures with at least one
dimension on the nanoscale’ (Xia, 2014: 12268) and therefore ‘the power of nanomedicine lies in its
ability to operate on the same molecular scale as the intimate biochemical
functions involved in the growth, development, and aging of the human body’
(Xia, 2014: 12269). However it is this power, derived from the complexity of
the potential interactions between synthetic nanomaterials and intimate
biological functions that has slowed the translation of nanomaterials to practical
medical application. Not only do desirable modes of action need to be
intimately understood, but the toxicity of nanomaterials must also be fully
addressed.
The development of nanomaterials for
healthcare is a particularly pressing question for the two of us (MPR and GLD),
as we both hold Fellowships from the Institute of Advanced Study at the
University of Warwick, focussed toward undertaking nanotechnology-based
research in the Department of Chemistry. With this concept in mind, we aimed to
organise a conference that would bring together researchers working to advance
the use of artificial nanomaterials in healthcare applications – giving rise to
the event “Emerging Nanomaterials for Healthcare”, which took place at the
University of Warwick on 28 November 2014. One of the great challenges in this
field is the number of traditional disciplines which the research typically
spans; from the physical understanding of the properties of nanoparticles, to
the chemistry of their fabrication, and the biology of their action as
therapeutic species. For this reason, a multi-disciplinary conference provided
an ideal forum for the exchange of ideas and expertise, as well as an
opportunity to develop the kind of collaborative research networks that are
vital for success in this field. We chose to invite seven speakers whose
expertise spanned a range of topics across synthetic chemistry, materials science
and biology and whose research shares the common goal of understanding and
developing tools to improve the diagnosis and treatment of disease for the
betterment of human health.
Synthetic chemistry is often divided
into two distinct disciplines; “organic chemistry” pertaining to man-made
compounds and materials which primarily contain those elements found in natural
organic matter (principally carbon, oxygen, hydrogen and nitrogen), and “inorganic
chemistry” which investigates compounds based on metallic elements (for example
iron, gold, cobalt and many more besides). Professor Nguyễn T.K. Thanh from
University College London used her talk to highlight some of her research group’s
efforts to fabricate a wide variety of inorganic particles with sub-100 nm
dimensions from metallic elements. Thanh demonstrated that her team have been
able to achieve control over both the size and shape of particles (with spheres,
cubes, rods, and even stars manufactured with incredible control over
reproducibility) as well as variations in particle surface coatings and the
layering of multiple metallic elements. Such metal nanoparticles have
applications in medical diagnosis; as their magnetic character can allow them
to function as contrast agents in magnetic resonance imaging (MRI), improving
the detection efficiency and therefore the quality of the images produced.
Thanh presented recent work where this tactic had been used to improve the
study of neural stem cell engineering, with the ultimate target of achieving
spinal cord reconstruction.
Dr Catherine Berry from the University
of Glasgow works very closely with biological cell lines, with the aim of
understanding how nanosized materials interact with human cells and tissues.
She presented work which utilises magnetic metal nanoparticles for “magnetofection”,
whereby clinicians would be able to control the movement of nanoparticles
through a patient’s body towards the area of diseased tissue (such as a tumour)
by using an external magnetic field. Research from the Berry group has focussed
on coupling this concept with the use of cell penetrating peptides (naturally occurring
signalling molecules that allow material to cross the cell membrane and enter
cells) so that the metal nanoparticles could be directed exclusively to
diseased cells and subsequently gain entry. Work in this field has the ultimate
goal of eliminating the unpleasant side-effects of chemotherapy, which result
from the non-specific action of cancer cell killing drugs thus resulting in the
simultaneous death of cancerous and healthy cells during treatment. This
strategy is a common theme in nanomedicine research, and indeed several other
speakers presented a variety of approaches to achieve the goal of specificity
in treatment.
In addition to using an external
stimulus, the presence of certain biomolecules or the natural differences in
the local environments between different areas of tissue and within cells can
also be exploited as a trigger for directed drug delivery. In his talk, Dr Seb
Spain from the University of Nottingham (now at the University of Sheffield) demonstrated
how nanoparticles can be designed to respond to specific deoxyribonucleic acid (DNA)
sequences. DNA is the building blocks of genes which contain the instructions
for the development and function of living organisms, and DNA communicates
these instructions by interacting with the biomolecules that make up the “machinery”
of the cell. Crucial to Spain’s research was the attachment of specific DNA
sequences to polymers; synthetic organic materials that can be designed to
mimic natural surfactants such as lipids (the main component of cell membranes)
in their ability to assemble into agglomerates on the nanometre scale. The
resulting hybrid DNA-polymer nanoparticles subsequently showed a response to
complementary DNA, which could therefore allow them to use the over expression
of certain DNA sequences (such as occurs in cancers) as a trigger for treatment
specificity.
As well as being targeted as an
indicator of disease, nucleic acids can also be utilised for therapy. The
presentation from Dr David Fulton of Newcastle University highlighted his
recent efforts to achieve the controlled delivery of nucleic acid therapeutic
agents using polymer nanoparticles. The assembly of polymers into particles on
the nanometre scale allows them to be loaded with a cargo, such as molecules of
a drug compound, while forming a protective layer around this cargo to prevent unwanted
clearance from the body by the immune system or the action of the kidneys. The
motive for using this well-established technique in Fulton’s research is the
attempt to improve the circulation time within the blood (and therefore the
potency) of cancer therapy which uses short interfering ribonucleic acids
(siRNAs). These siRNAs serve to silence the action of a particular gene, for
example those which are specific to the division and growth of cancer cells,
therefore leading to selective death of only the diseased cancerous cells.
Also focussing on the use of polymer
nanoparticles for drug delivery was Professor Marina Resmini from Queen Mary
University of London. Recent work from her group has concentrated on using
nanoparticles for transdermal drug delivery, which are topical treatments that
enter the body by crossing through the skin rather than by an oral or
intravenous administration. This is typically a challenging mode of action for
therapy, as the skin has evolved to provide a robust barrier against foreign
bodies in order to protect internal tissue from toxic and pathogenic materials.
The polymer nanoparticles developed by Resmini’s team were labelled with a
fluorescent dye, a material that absorbs light of higher energy (such as blue
light) and emits light of a lower energy (such as green light). This
fluorescent tag enabled the location of the nanoparticles to be tracked using
confocal microscopy (which couples conventional light microscopy with
fluorescence detection) following administration to the skin surface, allowing monitoring
of the passage of the nanoparticles across the skin, and their ultimate
distribution within the tissue below and hence a thorough understanding of
their behaviour and potential as delivery agents.
The challenge of advanced diagnosis
was addressed by the final two speakers. Dr Matthew Gibson and Daniel Phillips
from the University of Warwick both discussed how they have used hybrids of
metal (gold) nanoparticles, surface coated with organic polymers to create
sensors for diagnostic applications. In both cases the choice of gold
nanoparticles was motivated by the fact that they can be manipulated to give an
“easy to assess” visual readout. Due to an effect known as surface plasmon
resonance, a solution of gold nanoparticles will change colour if the
individual nanoparticles begin to agglomerate into clusters. Phillips exploited
this feature to produce a colorimetric test for levels of ferrous iron (Fe3+
ions), of interest due to the atypically high levels of Fe3+ linked
to a number of diseases, such as Alzheimer’s and Parkinson’s. Ferrous iron
sequestering units attached to a polymer immobilised onto the surface of gold
nanoparticles led to particle agglomeration in the presence of high levels of
Fe3+ ions, due to interparticle bridging. This resulted in the characteristic
colour change from the gold nanoparticles, thus providing a simple readout for
diagnosis. Gibson presented work that uses a similar approach for the detection
of bacterial toxins. In this case, the gold nanoparticle’s polymer shell can
selectively bind to the toxin (a model for highly poisonous “ricin”), which
again leads to particle agglomeration and the diagnostic colour change. As
Gibson explained in the introduction to his talk, the use of gold nanoparticles
in diagnostic tests is well established, with the Clearblue pregnancy test – arguably
the words most ubiquitous diagnostic test – based on similar technology. In
fact, as Xia points out ‘“nano” is
nothing new at all. Before it became a buzzword, people had already used
nanomaterials for many decades, if not centuries’ (Xia, 2014: 12268). Simple
and versatile chemistry such as that based on gold nanoparticles will inevitably
continue to find applications in emerging nanomaterials for healthcare.
The conference closed with our
speakers participating in a lively panel discussion, fielding questions from
the assembled delegates. Perhaps the most pressing issue raised was the
importance of working in collaborative research groups. Despite the majority of
the panel identifying as Chemists, there was a clear imperative to work in
collaboration with research groups possessing expertise in Biology, Life
Sciences, as well as clinicians and members of the pharmaceutical industry. In
the words of one panel member, ‘it is
important to avoid inventing challenges’ because they offer an opportunity
to do interesting chemistry, only to find that a problem never existed in the
first place. Instead, research should be directed by dialogue between the
various disciplines to identify a clear need in the first instance. Another
point on which the panel were agreed was the importance of testing materials in
biologically relevant conditions early in their development. For example, a
nanoparticle formulation intended as an intravenous treatment which is
insoluble in blood has no future, and it is essential to discover this sooner
rather than later. The panel discussion finished with the speakers suggesting
advances and directions for research that they hope to see tackled in the near
future. Answers included the desire for a standardised test for the efficacy of
drug release from nanoparticle delivery agents to enable comparison of data
obtained by researchers working on similar problems across the globe, and a
desire for a more complete understanding of the whole body immune system
response to nanoparticles, which must surely be required for nanomedicine to
become a clinical and commercial success.
The conference “Emerging Nanomaterials
for Healthcare” gave a great demonstration of the exciting possibilities for
synthetic nanomaterials to be applied to solve problems in healthcare. Talks
from our invited speakers, poster presentations from over twenty of the
delegates, and the panel discussion illustrated the strength and depth of
current nanomedicine research in the UK. We hope to see the field continue to
expand in the coming years, with increasing numbers of nanomaterial therapies
and diagnostics appearing in the clinic. As Xia concludes, ‘only when this relatively new and still seemingly bizarre realm of
nano is able to make a positive and long-lasting impact on every aspect of our
society, can we finally declare the arrival of the nano era’ (Xia, 2014:
12271).
We would like to extend our thanks to
the conference sponsors:
Institute of Advanced Study,
University of Warwick; Materials Global Research Priority, University of
Warwick; Materials Chemistry Division, Royal Society of Chemistry; Nanoscale
and Journal of Materials Chemistry B, Royal Society of Chemistry; the Polymer
Club, University of Warwick; ATG Scientific.
More details and photographs from the
“Emerging Nanomaterials for Healthcare” 2014 Meeting can
be found at http://warwick.ac.uk/enh2014.
References
Xia, Y.
(2014), ‘Are We Entering the Nano Era?’, Angew. Chemie Int. Ed., 53 (46), 12268-71
Stark, W. J.; Stoessel, P. R.;
Wohlleben, W.; Hafner, A. (2015), ‘Industrial applications of nanoparticles’, Chem. Soc. Rev., DOI: 10.1039/c4cs00362d