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Bio-nano interactions: new tools, insights and impacts

Event

Starts:

April
302014

09:00

Ends:

May
012014

17:00

Location

Kavli Royal Society Centre, Chicheley Hall, Newport Pagnell, Buckinghamshire, MK16 9JJ

Overview

Satellite meeting organised by Dr Michaela Kendall, Professor Kevin Kendall FRS, Professor Liam Grover and Professor Paula Mendes

Event details

Bionanotechnology is advancing to control and understand bio-nano interactions. New materials and devices are developed for applications, such as medicine. Influencing biology with nanoscopic materials provides opportunity to create innovative therapies or detect disease with unprecedented sensitivity, revealing the functions of cell components or molecules. Intracellular interference implies that toxicological risk should also be considered and avoided by safe design.

Download the meeting programme

Call for posters

To submit a poster to the organisers for inclusion in the meeting please email a title, 150 abstract and authors to the events team.

Biographies of the organisers and speakers are available below. Recorded audio of the presentations will be available on this page after the event.

Attending this event

This is a residential conference, which allows for increased discussion and networking. It is free to attend, however participants need to cover their accommodation and catering costs if required.

Enquiries: Contact the events team

Participants are encouraged to attend the related scientific discussion meeting which immediately precedes this event and is open to all.

Event organisers

Select an organiser for more information

Schedule of talks

Session 1: Biological control and monitoring using nanotechnology

4 talks Show detail Hide detail

Chair of session 1

Professor Paula Mendes, University of Birmingham

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Molecularly engineering cell-surface interfaces

Professor Pascal Jonkheijm, University of Twente, Netherlands

Abstract

Supramolecular chemistry provide nowadays an excellent prospect to construct reversible biological interfaces that can be employed for supramolecular cell manipulation experiments. Making use of supramolecular chemistry is rewarding to develop functional materials and devices. Knowing the limitations involved in ordering proteins at different length scales will surely hasten developing future applications, supramolecular bionanotechnology being the most prominent. The construction of synthetic supramolecular assemblies of proteins provides an excellent tool to fabricate organized bioactive components at surfaces. I will present new synthetic procedures for site-specific noncovalent anchoring of proteins to surfaces and polymers. Special attention is paid to orientational and conformational aspects at the surface and will be demonstrated. Using concepts of multivalency the interactions between proteins and surfaces can be modulated by design. Many of the protein complexes were patterned on surfaces using microcontact printing or nanolithography and visualized using fluorescence microscopy. Furthermore, supramolecular linkers that are sensitive to remote electrochemical stimuli will be presented, using cucurbituril (CB) and cyclodextrin (CD)-modified surfaces. Electrochemical switching was studied using surface embedded electrodes. Cell release was studied in detail in the case of cell-adhesive peptides and growth factors. Lastly, supramolecular linkers were compared to reversible covalent linkers, using imine chemistry, providing insight in the cell receptor signaling pathway. With the development of reversible bioactive platforms on surfaces serving as a reversible dynamic interfaces to cells, improved scaffolds for tissue regeneration will become in hand. First steps into this directions will be introduced as well.

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Nanoscale approaches to study bio-nano-interactions

Dr Matthew Dalby, University of Glasgow, UK

Abstract

The talk will review how cells, specifically mesenchymal stem cells, can exploit nanoscale information to control growth and differentiation. How cells perceive nanoscale information metabolically and genomically will be considered. The talk will also cover aspects of dynamic substrates to gain temporal control of stem cells and use of nano fibrous hydrogels to identify potential biological molecule mediators of stem cell differentiation.

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Electrochemical nano-bio-sensing of cells

Dr Frankie Rawson, University of Nottingham, UK

Abstract

The ability to monitor cellular events in real-time is paramount to advancing fundamental biological and clinical science. Recently, pioneering nano-electrochemical technology has been utilised to electrically wire cells but there are few examples of its utilisation for sensing of chemical pathways to aid in our understanding of cellular chemistry.

With this insight in mind studies will be presented describing the development of new nanotechnology based on electrodes nanostructured with single walled carbon nanotubes (SWCNTs) and electrocatalytic films.  The nanostructured sesnors were used to initially electrically “wire” non-electrogenic prokaryotic bacteria cells allowing for extracellular electrochemical communication. We were then interested in elucidating the pathways in which eukaryotic cell, namely yeast, shed electrons with the external environment. By carefully controlling the nano-topography of electrocatalytic modified surfaces we show for the first time that charge transfer events from the external surface of the cell wall of yeast could occur. Importantly, this electron transfer across the cell wall indicates that there is a need to redefine the function of the yeast cell wall.

We then utilised ITO electrodes nanostructured with SWCNTs to intracellularly “wire” macrophage cells[1].  This cell-nanosensor construct was further  modified by functionalising the SWCNTs with an electrocatalyst to enable the selective real-time monitoring of reactive oxygen species (ROS).  The developed nanosensor was used to provide new insight into the early cell signalling mechanisms underpinning an immune cells response to an endotoxin.  This electrochemical nanotechnology provides a generic platform that can be easily tailored, yielding new sensing tools for biologists investigating intracellular nanochemistry (Fig 1).

(1)         Rawson, F J; Yeung, C L; Jackson, S K; Mendes, P M Nano Letters 2013, 13, 1.

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Session 2: Therapeutic potential of nanotechnology

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Chair of session 2

Professor Liam Grover, University of Birmingham, UK

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Nanoparticle fabrication for therapeutic delivery

Professor Matthias Epple, University of Duisberg-Essen, Germany

Abstract

Inorganic nanoparticles can be used to carry therapeutic biomolecules in the body and into cells. Applications of biodegradable calcium phosphate nanoparticles will be highlighted. These can be prepared in a multi-shell way to protect incorporated biomolecules from enzymatic degradation and also surface-functionalized, e.g. with antibodies, for specific cell targeting. We have successfully used such nanoparticles for the delivery of DNA (transfection), of siRNA (gene silencing), and of antigens/TLR ligands (stimulation of the immune system). The addition of fluorescing molecules allows totrack their pathway into cells and also in the body.

As a second example, silver nanoparticles which are increasingly used as antibacterial agent in biomedicine and in consumer products are discussed. We have shown that their bactericidal action is due to released silver ions after oxidative dissolution, and that the therapeutic window between bacteria and mammalian cells is unexpectedly narrow.

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Engineering instructive biomaterials for tissue regeneration: a matter of right tools

Professor Pamela Habibovic, University of Twente, Netherlands

Abstract

Synthetic substitutes for skeletal tissue, such as bone and cartilage, present a potentially interesting alternative to patient’s own tissue and strategies based on biological growth factors and/or cells, because they are relatively inexpensive, off-the-shelf available and adaptable to requirements of individual clinical application. Nevertheless, synthetic biomaterials are still not considered a valid and comprehensive alternative to natural grafts.

In order to improve clinical performance of synthetic biomaterials in skeletal tissue regeneration, one needs to look for tools outside the toolbox of a classical biomaterials scientist and design properties of biomaterials instead of simply relying on production parameters. Here, a number of such tools is discussed, including micro- and nanotechnology methods to separate chemistry from topography, application of microfluidics to increase throughput and complexity of screening material properties and application of bioinorganics as synthetic “growth factors”. In addition, it is elaborated on challenges one needs to deal with in the process of applying micro- and nano-engineering tools to large, 3D functional implants with clinical relevance.

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Towards bioengineered control of cell fate post transplantation

Dr Jeff Karp, Brigham and Women's Hospital - Harvard Medical School, USA

Abstract

Control of cell fate and its extracellular environment is critical for tissue regeneration and cell therapy. This talk will explore methods to enhance the engraftment of systemically infused stem cells through engineering the cell surface to induce a robust rolling response. This approach is based on leukocytes ability to target tissues via specific interactions with the vascular endothelium. In addition, a strategy to engineer cells with an intracellular depot of phenotype altering agents will be described that can be used for drug delivery or programming cell fate via both intracrine-, paracrine-, and endocrine-like mechanisms. The talk will also examine the potential of cell surface sensors that can be used to detect signals within the cellular nano-environment with unprecedented spatial and temporal resolution. This should be useful for monitoring the cell secretome following transplantation, for drug discovery and for elucidating niche biology in vivo.

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Session 3: Human bio-nano interactions: what we know

6 talks Show detail Hide detail

Chair of Session 3 & 4

Dr Michaela Kendall, University of Southampton, UK

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Nanoparticles entering the human lung

Professor Howard Clark, University of Southampton, UK

Abstract

The lung surfactant system is a complex lipoprotein mixture which lines the alveoli of the lungs and reduces surface tension, preventing lung collapse on exhalation. It has become clear that this surfactant layer also acts in defence of the lung from inhaled potentially injurious or toxic materials including microbes, allergens and nano particulate pollutants. We have described how components of surfactant, specifically surfactant proteins A and D , interact with nanoparticles and shown that nanoparticles interact differently with lung surfactant depending on their surface chemistry. Surfactant proteins are critical regulators of lung inflammation and we show how disruption of their function by nanoparticles may affect their efficiency in protecting the lung from inflammation and infection. By subverting these natural defence mechanisms of the lung, nanoparticles may persist in the respiratory tract, translocate into the circulation and potentially contribute to both respiratory and systemic disease.

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Nanoparticles in the gastrointestinal tract: exposure, absorption and utilisation are normal physiological processes but imposters take advantage

Dr Jonathan Powell, MRC HNR, UK

Abstract

There are, in fact, purposeful pathways for nanomineral uptake in the gastrointestinal tract, probably for nutritional and immunological reasons. Regular epithelial cells can endocytose very fine (< 10nm) nanoparticles and this is exemplified by iron oxo hydroxide, derived from various dietary/digested sources, in the proximal small bowel yielding desirable iron absorption. For larger nanoparticles the more specialised particle-scavenging M-cells of gut lymphoid follicles are the portals of entry. Particle sizes of 20-250 nm appear to be optimal for nanoparticle uptake via this route. The naturally occurring process revolves around mineralised calcium: more so, we believe, for immunological than nutritional processes. However, recent ‘nano additions’ to the human diet- namely excipients in drugs or nutraceuticals or even toothpaste, as well as nanomineral food additives- can be seen to hijack this important M cell entry point: these imposters are not yet associated with human disease but will this always be the case?

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What data we have to support the use of predictive modeling and alternative strategies for regulatory decision making

Professor Andre Nel, UC Center for the Environmental Impact of Nanotechnology, USA

Abstract

Nanotechnology introduces a new field requiring novel approaches and methods for hazard and risk assessment.  In order to perform safety assessment, nanoscale properties and the functionality of engineered nanomaterials (ENMs) at the nano/bio interface are important considerations.  This rapidly advancing field requires novel test strategies that allow multiple toxicants to be screened in robust, mechanism-based assays in which the bulk of the investigation can be carried out at the cellular and biomolecular level while limiting animal use that is based on the contribution of pathways of toxicity to the pathophysiology of disease. First, a predictive toxicological approach for the safety assessment of ENMs will be discussed against the background of a ‘21st century vision’ for using alternative test strategies (ATSs) to perform toxicological assessment of large numbers of toxicological substances. ATS is defined here as an alternative to animal experiments or refinement/reduction alternative to traditional animal testing.  Secondly, the approach of selecting pathways of toxicity to screen for the pulmonary hazard potential of carbon nanotubes, metal oxides, and silica will be discussed, as well as how to use this information to perform high-content or -throughput screening.  I will also describe how the data could be used for hazard ranking, risk assessment, regulatory decision-making and ‘safer-by-design’ strategies.

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The challenge of nanotechnology's revolutionary change: emerging international laws

Dr Ilise L Feitshans, University of Lausanne, Switzerland

Abstract

Nanotechnology has been heralded as a revolution by scientists and policymakers since 2008. Its new view of the physical properties of matter combined with the new investments it has unleashed are a major shot of adrenalin in an ailing global economy, and its promises of new medicines, lighter packaging and cheaper transport of goods offer miraculous promises for public health. Yet, the dangers of using well –established toxins and even previously innocuous substances at the nanoparticle level are unknown. Governments and policymakers are unwilling to commit to stating that nanotechnology applications in products are safe, despite their cognizance of their obligation to protect public health. Consequently, every nation and many regional organizations have created draft nanotechnology regulations. Where will this lead? It is reasonable to envision an international convention before the General Assembly of the United Nations (UN) but what can be accomplished by any new laws remains uncertain without key steps towards international harmonization. This presentation explores key regional laws impacting the UK in Council of Europe and the European Union, and discusses the pivotal role that UK can play towards international harmonization of nanotechnology regulations

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Dr Iseult Lynch, University of Birmingham, UK: From bionanoscience to regulation and law – opportunities and challenges

Dr Iseult Lynch, University of Birmingham, UK

Abstract

Scientists are increasingly called upon to ensure that their scientific research has wider societal impact, with nanosciences and nanotechnologies a case in point.  In parallel with imagining and developing ever more innovative new materials and applications of these materials in everything from consumer products such as cosmetics, clothing and food to industrial applications such as self-healing construction materials, stronger and lighter materials for aviation and automotive industries and indeed in medicine, where their small size and “access all areas” potential has lead to them be hyped as magic bullets to address a range of currently intractible diseases, there is a need to ensure that all these developments are safe for society.  Indeed few technologies have had such an ethos of safe and responsible development embedded into the researchers psyche from such an early stage of development, but then few technologies are so far-reaching in their potential.   
 

An ongoing challenge in this new world order is for researchers to learn the lingo of those who translate scientific data into the policy, regulation and legal frameworks that ensure our safety, health and economic well-being.  This is especially challenging in emerging fields, where knowledge is patchy, rapidly evolving and often utilising tools and approaches that were designed for other purposes.  Safety assessment of nanomaterials is hampered by all of these issues and more – its multi-disciplinarity as a science means that researchers also have to learn to communicate across scientific boundaries, with materials scientists and engineers needing to interact with biologists, medics and toxicologists.  Thus, what is common knowledge, indeed old-hat in one field, is unknown and painfully re-discovered in another, leading to (unnecessary?) errors in the scientific literature, irreproducibility of results (for often silly reasons) and increased confusion among the policy, regulatory and legal communities.  So how can we move forward to ensure a more coherent approach to science to policy (i.e. regulation and/or law) communication?  A suggestion is that we use the very disruptiveness of nanotechnologies to allow us to spotlight the challenges and provide an opportunity to reframe the approaches to such cross-stakeholder (cross-sectoral?) communications in the same way that the science of nanosafety is spotlighting inadequacies in existing scientific and regulatory approaches and offering new ways forward.

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Session 4: The implications of bio-nano interactions for society

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Chair of Session 3 & 4

Dr Michaela Kendall, University of Southampton, UK

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Nanotechnology Safe-by-Design: old meets new, but which is which?

Dr Steffi Friedrichs, Nanotechnology Industries Association, UK

Abstract

The concept of ‘Safe by Design’ (or ‘Safer by Design’ to be more precise, but by no means accurate, for both the safety or increase thereof of a specific product are highly subjective attributes that vary with the application of a product, as well as with the complex opinion forming process of the beholder) is nothing new to those driving and implementing innovation; neither is it something that indicates that products that were designed before the term was created had not been developed with the requirement of safety in mind, nor is it a reason to consider those products ‘unsafe’.

The challenges arising from the increasingly loud calls for the development of nanotechnologies under the ‘Safe by Design’ concept, as it is mainly driven by policy-makers and supported by those that celebrate nanotechnology for the provision of evermore accurate analytical tools and material engineering methodologies, are manifold and only some of those challenges are nano-specific: like in many other areas, such as regulation, policy and ethics, nanotechnology-enabled innovations have become examples and demonstrators of the limitation of the current practices and established processes, such as regulatory risk assessment.

This presentation will highlight some of the barriers to the adoption of ‘Safe-by-Design’ in the development of nanotechnologies and discuss solutions to overcoming these, sometimes provided by nanotechnologies themselves.

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Innovative approaches to emergent risks

Professor Andrew Maynard, Risk Science Center, University of Michigan, USA

Abstract

Over the past decade, nanoscale science and engineering have been associated with tremendous progress in research and innovation.  In particular, new understandings of material-biology interactions have helped catalyze technological advances, and provide insights into emergent risks and potential management strategies.  The field has also stimulated the development of novel frameworks for responsible research and innovation.  Yet successful as the nanotechnologies enterprise has been, there have been mis-steps and missed opportunities in developing safe and successful applications of emerging technologies.  

In particular, as increasingly sophisticated technologies continue to emerge from research at the nano-bio interface, there are lessons from the past decade that provide valuable insight into the sustainable development of future technologies and products.  These include avoiding “lock in” to technological assumptions when exploring emergent risk; proactively exploring key potential impacts; embracing stakeholder engagement; and approaching technology benefits and impacts from within the bounds of plausible outcomes.  

In the specific context of nano-biotechnology, past experience indicates research addressing potential risks and rewards needs to be underpinned by appropriate framing and parameterization of critical challenges, and an emphasis on plausibility when exploring future scenarios.  There also a pressing need for innovative approaches to integrated risk assessment and management frameworks.

  

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Nanotechnology: balancing benefits and risks

Tanja E J Kleinsorge, Parliamentary Assembly of the Council of Europe

Abstract

The Council of Europe is the continent’s leading human rights organisation. It is also a world-leader in bio-ethics with the landmark Convention on Human Rights and Biomedicine, short “Oviedo Convention”, which is in force in the majority of the Council’s 47 member states.

In April 2013, the Council of Europe’s Parliamentary Assembly voted a report on “Nanotechnology: balancing benefits and risks to public health and the environment”, which had as its central recommendation that the Committee of Ministers work out guidelines in this field. These guidelines could first take the form of a recommendation, but could also be transformed into a binding legal instrument if the majority of member States so wished, and be used as a model for regulatory standards worldwide.

In December 2013, the Committee of Ministers agreed that the Council of Europe’s Committee on Bioethics be entrusted with a feasibility study on the elaboration of possible standards in this area – this study will start in May 2014. It will examine the scientific and ethical challenges raised by emerging technologies, including nanotechnology, and analyse the implications for human rights of these technologies and their applications in the biomedical field with a view to drafting a possible white paper.

 

 

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Bio-nano interactions: new tools, insights and impacts Kavli Royal Society Centre, Chicheley Hall Newport Pagnell Buckinghamshire MK16 9JJ