Wireless communication with cells towards bioelectronic treatments of the future
Lead Research Organisation:
UNIVERSITY OF NOTTINGHAM
Department Name: School of Pharmacy
Abstract
Electroceutics, or bioelectronic drugs are defined as treating disease via control of the body's electrical signals and are the future therapeutic intervention. Examples of electroceutic devices include the cochlear implant, retinal implants forming a bionic eye, pace maker for modulating heart rhythm, deep brain stimulators for treating Parkinson's and other neurological disorders, and most recently a wraparound vagus nerve stimulator to treat arthritis. They rely on electrical stimulation of neuronal pathways that cause a functional effect to treat a disease or an ailment. Bioelectronic based therapies typically involve the merging of electronic devices with neuronal cells/tissues. This generally involves initial invasive surgery for implantation of the electronic component which also needs regular replacement. The electronic components of the device stimulates nerves cells/tissues in an unprecise manner. However, whilst treating disease by modulating neural relays has been the focus of research, almost no studies exist describing bioelectronic based therapies for non-neuronal cells. This is surprising considering all cells are electrically active. The field of electroceutics is an emerging strategy as an important method for disease intervention and will be increasingly important in the management of human disease. In order for electroceutical therapies to fulfil their potential there are still a number of challenges to be solved. These include
*A more thorough understanding of how cellular electrical talk malfunctions underpin disease, and a more targeted approach in modulating the cellular-electrical relays that underpin sickness.
*A broadening of electroceutical therapeutic intervention from nervous system application as well as other cell and tissue types.
*A need to avoid invasive surgery thereby making the technology more adaptable via development of wireless technology.
The research proposed will work towards addressing these challenges by developing new electrochemical based wireless technology, which may avoid invasive surgery and will be applied to treating non-neuronal based diseases such as cancer. In addition, by combining 3D printing of electrochemical systems with the wireless cellular actuation, we plan to be able to target and control specific neuronal circuits. The research exploits concepts and tools from electrochemistry, nanochemistry, supramolecular chemistry, additive manufacturing and bionanotechnology to develop electrochemical based wireless nanotechnology to sense and actuate cellular behaviour. By bringing to fruition the application of electrochemistry to electroceutics in developing such novel disruptive technology it will significantly advance healthcare technology. In addition it will make a profound and significant impact in the broad fields of biosensors applications in many areas such as biomedical diagnostics, pharmaceutical industry, defence and environmental monitoring and offer new research tools to study cellular electrochemistry.
*A more thorough understanding of how cellular electrical talk malfunctions underpin disease, and a more targeted approach in modulating the cellular-electrical relays that underpin sickness.
*A broadening of electroceutical therapeutic intervention from nervous system application as well as other cell and tissue types.
*A need to avoid invasive surgery thereby making the technology more adaptable via development of wireless technology.
The research proposed will work towards addressing these challenges by developing new electrochemical based wireless technology, which may avoid invasive surgery and will be applied to treating non-neuronal based diseases such as cancer. In addition, by combining 3D printing of electrochemical systems with the wireless cellular actuation, we plan to be able to target and control specific neuronal circuits. The research exploits concepts and tools from electrochemistry, nanochemistry, supramolecular chemistry, additive manufacturing and bionanotechnology to develop electrochemical based wireless nanotechnology to sense and actuate cellular behaviour. By bringing to fruition the application of electrochemistry to electroceutics in developing such novel disruptive technology it will significantly advance healthcare technology. In addition it will make a profound and significant impact in the broad fields of biosensors applications in many areas such as biomedical diagnostics, pharmaceutical industry, defence and environmental monitoring and offer new research tools to study cellular electrochemistry.
Planned Impact
During the proposed project we will develop a wireless based electrochemical bioelectronic therapeutic. The technology will provide a completely new approach to treating cancer and potentially diseases that are underpinned by neuro dysfunction. The research outcomes will have a far reaching and diverse impact within the medical, pharmaceutical, biomedical, scientific and industrial communities. The researchers, academics and industrial partners involved will benefit through participation in an internationally leading research effort and help to define the newly emerging area of bioelectronic approaches to therapeutics. The Post-doctoral researchers and PhD student recruited through this project will have unique training to contribute and lead the blossoming industry of bioelectronics. The project will develop researcher skills in three key areas: 3D printing coupled with nano-wireless fabrication of multidimensional bio-functional systems, development of new bioelectronics and new nanotechnology. These are areas that are key for future development of new electroceutics which is a focus for growth in the UK and where there is a demonstrable need for multidisciplinary new high level skill sets. The underpinning technology will provide a platform for research into innovative bioelectronics, as well as providing researchers new tools from other disciplines because they can create new sensors and actuators for their research field. This will impact on researchers in fields of cell biology, environmentally sensing and agrochemical.
UK industry will benefit through new research that further enhances the UK's leading position in bioelectronics with GSK being the pioneers. The research will impact existing products and new product conception and realisation, with corresponding economic, societal, healthcare and environmental benefits. Pharmaceutical companies and diagnostics companies involved in the project will benefit economically. Other industries such as the electronic industrial capacity will also benefit because we will 3D print unique conductive geometries and ensure new capabilities of printing 3D electronics which are not currently possible. Additive manufacturing is currently an expanding UK industry whilst the research efforts are concurrently broadening and deepening to multi-functional / multi-material systems is approaching a cliff-edge where insufficient human capital will be available to maintain the UK lead. This project will contribute to reducing this people deficit in this field by training and developing the researchers involved in the project and the core skills that are required to develop bioelectronics and additive manufacturing technology both academically and industrially.
Society will benefit through the expedited realisation of advanced multifunctional bioelectronics devices which will have multi-sectoral benefits from improved healthcare devices and treatment options. The healthcare system will benefit through the genuine advancement in technologies which have the capability to help deliver on the need for advancements in healthcare and advanced pharmaceutical/medical devices, helping alleviate current, and the inevitable future demands on healthcare services.
The tailored support package offered by the University of Nottingham will ensure Dr Rawson leads this area to material outcome by developing new state of the art electroceutics which will impact on future healthcare technology and improve patient outcomes as the technology will be less invasive than that currently used. In the long term this will result in new non-invasive healthcare technology for cancer therapies and neuronal dysfunction. In addition the new team formed which includes Chemists, Biologists, Engineers and Clinicians ensures that the knowledge and expertise is readily adaptable to drive these new tools to market.
UK industry will benefit through new research that further enhances the UK's leading position in bioelectronics with GSK being the pioneers. The research will impact existing products and new product conception and realisation, with corresponding economic, societal, healthcare and environmental benefits. Pharmaceutical companies and diagnostics companies involved in the project will benefit economically. Other industries such as the electronic industrial capacity will also benefit because we will 3D print unique conductive geometries and ensure new capabilities of printing 3D electronics which are not currently possible. Additive manufacturing is currently an expanding UK industry whilst the research efforts are concurrently broadening and deepening to multi-functional / multi-material systems is approaching a cliff-edge where insufficient human capital will be available to maintain the UK lead. This project will contribute to reducing this people deficit in this field by training and developing the researchers involved in the project and the core skills that are required to develop bioelectronics and additive manufacturing technology both academically and industrially.
Society will benefit through the expedited realisation of advanced multifunctional bioelectronics devices which will have multi-sectoral benefits from improved healthcare devices and treatment options. The healthcare system will benefit through the genuine advancement in technologies which have the capability to help deliver on the need for advancements in healthcare and advanced pharmaceutical/medical devices, helping alleviate current, and the inevitable future demands on healthcare services.
The tailored support package offered by the University of Nottingham will ensure Dr Rawson leads this area to material outcome by developing new state of the art electroceutics which will impact on future healthcare technology and improve patient outcomes as the technology will be less invasive than that currently used. In the long term this will result in new non-invasive healthcare technology for cancer therapies and neuronal dysfunction. In addition the new team formed which includes Chemists, Biologists, Engineers and Clinicians ensures that the knowledge and expertise is readily adaptable to drive these new tools to market.
Organisations
- UNIVERSITY OF NOTTINGHAM (Lead Research Organisation)
- Lawrence Livermore National Laboratory (Collaboration, Project Partner)
- Abiel Biotech (Collaboration)
- University of Minnesota (Collaboration)
- SureScreen Diagnostics Ltd (Project Partner)
- University of Minnesota (Project Partner)
- University of Melbourne (Project Partner)
- University of Barcelona (Project Partner)
Publications
Sherman HG
(2018)
New Perspectives on Iron Uptake in Eukaryotes.
in Frontiers in molecular biosciences
Sanjuan-Alberte P
(2019)
Engineering the spark into bioelectronic medicine.
in Therapeutic delivery
Vaithilingam J
(2019)
Multifunctional Bioinstructive 3D Architectures to Modulate Cellular Behavior
in Advanced Functional Materials
Bruce G
(2019)
Singlet oxygen generation from porphyrin-functionalized hexahedral polysilicon microparticles
in Journal of Porphyrins and Phthalocyanines
Sanjuan-Alberte P
(2019)
Remotely Controlled in Situ Growth of Silver Microwires Forming Bioelectronic Interfaces.
in ACS applied materials & interfaces
Hicks JM
(2019)
Real-time bacterial detection with an intracellular ROS sensing platform.
in Biosensors & bioelectronics
Sherman HG
(2019)
Mechanistic insight into heterogeneity of trans-plasma membrane electron transport in cancer cell types.
in Biochimica et biophysica acta. Bioenergetics
Sherman HG
(2019)
Mammalian-Cell-Driven Polymerisation of Pyrrole.
in Chembiochem : a European journal of chemical biology
Sanjuan-Alberte P
(2019)
Wireless Nanobioelectronics for Electrical Intracellular Sensing
in ACS Applied Nano Materials
Shaw A
(2019)
Wireless Bioelectronics Towards Treatment of Glioblastoma Multiforme
in Neuro-Oncology
| Title | Electric Field Induced Biomimetic Transmembrane Electron Transport Using Carbon Nanotube Porins (Small 32/2021) |
| Description | Journal Front Cover |
| Type Of Art | Image |
| Year Produced | 2021 |
| Impact | Incraesed vision of the work |
| URL | https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202170164 |
| Title | Pod Cast |
| Description | Interview with MRS |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| Impact | Enhanced audience knowledge |
| URL | https://www.stitcher.com/show/mrs-bulletin-materials-news-podcast/episode/episode-24-gold-nanopartic... |
| Description | This award helped us develop a new way of using extremely small conductive particles and materials as wireless electrical bridges in biological systems. In simple terms, we showed that it is possible to influence and measure electrical and chemical behaviour at the nanoscale without needing conventional wires attached directly to the material. This matters because living cells rely on electrical signals, including membrane potential, to control essential functions such as communication, growth and survival, but current technologies for interacting with these signals are often too invasive or too limited for use in complex biological environments. A key achievement of the work was showing that nanoscale materials can be remotely polarised by an external electric field and used to trigger or report electrochemical changes in their surroundings. This established the foundations of bipolar nanoelectrochemistry as a new wireless bioelectronic approach. Importantly, the research also supported the idea that quantum biological effects, such as electron tunnelling across very small distances, can play a role in how these systems interact with biology. This opens up new ways of thinking about how electrical signalling can be controlled in living systems at the molecular level. These advances are particularly relevant to diseases such as glioblastoma multiforme (GBM), an aggressive brain cancer with very limited treatment options. Our work has helped provide the scientific basis for approaches that could one day be used to alter membrane potential and associated cellular signalling in cancer cells, with the aim of influencing cell behaviour and triggering therapeutic responses such as apoptosis. More broadly, the research has laid the groundwork for future healthcare technologies based on wireless sensing and modulation, including applications in cancer, inflammation, and other diseases where electrical signalling is important. |
| Exploitation Route | The outcomes of this funding can be taken forward in several ways by researchers, clinicians and industry. First, other academic groups can build on the bipolar nanoelectrochemistry platform to better understand how electrical signals, membrane potential and electrochemical processes influence cell behaviour in health and disease. This is especially relevant in areas such as cancer, inflammation, regenerative medicine and bioelectronic medicine. Second, the work provides a foundation for others to develop new healthcare technologies based on wireless sensing and modulation. For example, the principles established here could be used by researchers and commercial partners to design less invasive tools for detecting disease markers, monitoring biological responses in real time, or delivering targeted electrical-molecular therapies. The findings are particularly relevant to diseases such as glioblastoma, where there is a need for new approaches that can influence cancer cell behaviour more precisely. Third, the research may be taken forward through interdisciplinary collaboration between universities, the NHS and healthcare technology companies. Further development could include optimisation of the materials, testing in more advanced biological models, integration into device formats, and eventual translation towards clinical applications. More broadly, the award has created enabling knowledge rather than a single end product. Its main value is that it provides a scientific and technological platform that others can now adapt, refine and apply across a range of biomedical challenges. |
| Sectors | Electronics Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | Dr. Frankie Rawson's recent breakthroughs in the field of wireless communication with cells herald a significant advancement, with the potential to revolutionise bioelectronic treatments and the broader scientific and medical communities. This research, centring on the ability to wirelessly communicate and control cells, not only paves new pathways for treating various diseases and conditions but also introduces the world's first quantum-based therapeutic, marking a new era in technological advancement. The wider impact of this grant is seen through several lenses: Economic and Societal Impacts Global Economic Performance and UK Economic Competitiveness: The development of the world's first quantum-based therapeutic represents a leap in biotechnology and healthcare, enhancing the growth of these industries not only in the UK but globally. As these quantum technologies progress and reach commercialisation, they are poised to enhance the UK's standing as a leader in innovative healthcare solutions, attracting significant investment and fostering economic growth. Effectiveness of Public Services and Policy: Quantum-based bioelectronic treatments could revolutionise public health policies by offering new, highly effective treatment modalities for chronic diseases, potentially reducing healthcare costs and improving patient outcomes. This could lead to a more strategic allocation of resources within public health services and the formulation of health policy based on the latest, cutting-edge scientific discoveries. Quality of Life, Health, and Creative Output: The advent of quantum-based therapies promises targeted treatments with minimal side effects, significantly enhancing patients' quality of life. Diseases once considered untreatable or challenging to manage could become manageable or even curable, with profound positive impacts on global health outcomes. Moreover, this interdisciplinary research-bridging the gaps between biology, quantum physics, engineering, and information technology-stimulates creative solutions that could inspire innovations across multiple sectors beyond healthcare. Academic Impact Nucleation of New Research Areas: Dr. Rawson's pioneering work in quantum-based cellular communication is poised to nucleate new fields of study, fostering interdisciplinary research that merges life sciences with quantum technology and engineering. This approach could lead to further scientific breakthroughs, deepening our understanding of cellular mechanisms and their applications in medicine and other areas. Breakthrough in Fundamental Research Challenges: Overcoming the fundamental challenge of wireless communication with cells through quantum technology represents a monumental scientific breakthrough. This innovation not only opens the door to cutting-edge treatments but also significantly enhances our understanding of cellular processes. The implications for how we study cells and their interactions could lead to discoveries with far-reaching impacts beyond the initial focus of bioelectronics. In summary, the impact of Dr. Frankie Rawson's research extends far beyond the immediate academic achievements, promising substantial benefits to the economy, society, and the continued advancement of science. By introducing the world's first quantum-based therapeutic, this work not only lays the groundwork for a new era of bioelectronic medicine but also exemplifies the transformative potential of research that crosses traditional disciplinary boundaries. It offers hope for future innovations that could dramatically improve human health and wellbeing, showcasing the UK's leading role in pioneering healthcare technologies. |
| First Year Of Impact | 2023 |
| Sector | Government, Democracy and Justice,Other |
| Impact Types | Societal |
| Description | BBSRC international Partnership |
| Amount | £20,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2022 |
| End | 03/2023 |
| Description | EPSRC Early Career Equipment block grant |
| Amount | £100,000 (GBP) |
| Organisation | University of Nottingham |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2019 |
| Description | Enablement Grant |
| Amount | £10,000 (GBP) |
| Funding ID | E21-1135058786 |
| Organisation | Royal Society of Chemistry |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2021 |
| End | 08/2022 |
| Description | Quantum Medicine Approach to Treat Cancer |
| Amount | £65,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2023 |
| End | 12/2023 |
| Description | Abiel (Biotechnological company) |
| Organisation | Abiel Biotech |
| Country | Italy |
| Sector | Private |
| PI Contribution | Guidance on performing in vivo studies with our developed technology. |
| Collaborator Contribution | Expertise in performing in vivo experimentation |
| Impact | The collaboration is multidisciplinary and covers Pharmacists, Bioelectronics and clinical expertise. |
| Start Year | 2022 |
| Description | Prof A Now, LLNL |
| Organisation | Lawrence Livermore National Laboratory |
| Country | United States |
| Sector | Public |
| PI Contribution | A postdoctoral researcher visited Alex's lab and provided biological expertise and knowhow in performing cell experiments. |
| Collaborator Contribution | Alex provided training in how synthesis short CNT porins in cells and liposomes. This knowledge and expertise in building the rig to facilitate this has been transferred back to Nottingham. |
| Impact | Poster Presentation: Gordon Research Conference 2019, USA Probing, Manipulating and Understanding Cell-Materials Interfaces to Achieve Electrical Continuity Poster Presentation: Asilomar Bioelectronics Symposium 2019, California, USA Oral Presentation: Elecrtochem 2019, UK |
| Start Year | 2018 |
| Description | Prof Mike Mcalpine, University of Minnesota |
| Organisation | University of Minnesota |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We provided know-how on forming conductive materials for 3D printing of extracellular matrix towards building 3D-bioelectronic devices. |
| Collaborator Contribution | Mike provided intellectual input and access to specialized additive manufacture equipment. A 6-month placement by one of the Post Doctoral researchers was undertaken in Mike's lab and knowledge transfer occurred when the candidate returned to Nottingham. |
| Impact | This is a multi-disciplinary collaboration with Minnesota providing engineering expertise combined with pharmaceutical and biological expertise from Nottingham. |
| Start Year | 2019 |
| Title | Redox Nanoparticles for Quantum Medicine |
| Description | REDOX NANOPARTICLE FIELD The present invention relates to a nanoparticle , and in particular but not exclusively to a nanoparticle for modulating a redox state of molecules, and use of the nanoparticle for treating cancer. BACKGROUND Cells modulate their function through the control of electrical currents which are essential to life. Bioelectricity (defined as the electrical language of cells) is essential for biological function. The cell is increasingly accepted as a mass of bioelectrical interconnected circuits. One of the most well-known electron transfer pathways is photosynthesis and was one of the first whose mechanism was linked to quantum mechanical effects. It has been reported that cyt c can induce apoptosis when its redox state is modulated through an electron transfer process at the heame. This can occur via electron tunnelling and was shown in occur inside cells. However, the ability to electrically communicate with such biological systems is limited by current communication technology. Technology to date has failed to achieve on -demand targeted electrical-molecular communication within cells. This is because current communication technology is not appropriate for merging with cells at a spatial/temporal level equivalent to the native biological communication that occurs. The present invention has been devised with the foregoing in mind. SUMMARY According to a first aspect, there is provided a conductive nanoparticle, comprising an electron donor species and an electron acceptor species each attached to the nanoparticle . It has recently been shown that conductive objects such as gold nanoparticles and carbon nanotubes can act as bipolar nanoelectrodes within cells when external electric fields are applied. These bipolar nanoelectrodes, on the application of an electric field, become polarised. This leads to a potential gradient across the particle. If the potenti al difference at the poles of the particle is sufficiently large, this can provide the thermodynamic driving force to cause electrochemical -induced redox reactions. These redox reactions occur at the surface/solution interface of the nanoparticle and surrounding media. Advantageously, the present invention may enable the redox state of the electron donor species and/or the electron acceptor species to be controllably modulated by applying an electric field to the nanoparticle. In turn, by controlling the redox state of the electron donor species and/or the electron acceptor species, cell-specific signalling pathways such as apoptosis may be actuated by the change in redox state. The electron donor species and the electron acceptor species may be configured to enable electron transfer between one another in response to application of an electric field. The electron donor species and the electron acceptor species may be configured to enable electron transfer between one another by electron tunnelling in response to an electric field. The electric field may be an AC electric field. The electric field may have a frequency of between about 1 MHz and about 5 MHz, and optionally between about 1 MHz and about 3 MHz. Additionally or alternatively, the electric field may have a strength of between about 0.25 V/cm and about 1.5 V/cm, optionally between about 0.5 V/cm and about 1.25 V/cm, optionally between 0.6 V/cm and about 1.0 V/cm, optionally between about 0.6 V/cm and about 0.8 V/cm, and optionally about 0.65 V/cm. The nanoparticle may be or comprise a metallic nanoparticle, for example, a gold nanoparticle. Alternatively, the nanoparticle may be or comprise a carbon nanotube. The nanoparticle may have a size, for example a diameter, of between about 50nm and about lOOnm. The electron donor species may be or comprise a redox protein. The electron donor species may be or comprise an oxidoreductase enzyme. The electron donor species may be or comprise cytochrome c. The electron acceptor species may be a redox active molecule. The electron acceptor species may be or comprise porphyrin. The electron acceptor species may be or comprise zinc porphyrin. At least one of the electron donor species and the electron acceptor species may be attached to the nanoparticle by a linker. The linker may be or comprise polyethylene glycol. The linker may have a molecular mass of between about 1000 Da and about 3500 Da, optionally between about 1000 Da and about 2000 Da. The linker may have a molecular mass about 1000 Da, or about 2000 Da, or about 3500 Da. The linker may have a length of between about 1.5nm and about 7.5nm, optionally between about 1.5nm and about 5nm. The linker may have a length of between about 1.5nm and about 2.5nm, or between about 3nm and about 5nm, or between about 6nm and about 7.5nm. The length of the linker may refer to a distance between the nanoparticle and a respective one of the electron donor species and electron acceptor species when the electron donor species or the electron acceptor species is attached to the nanoparticle by the linker. The distance may be between an outer surface of the nanoparticle where the linker is attached to the nanoparticle, and a part of the respective one of the electron donor species and electron acceptor species that is attached to the linker. The nanoparticle may be a gold nanoparticle, the electron donor species may be or comprise cytochrome c, the electron acceptor species may be or comprise zinc porphyrin, and the electron donor species and the electron acceptor species may be attached to the nanoparticle by a polyethylene glycol linker having a molecular mass of between about 1000 Da and about 2000 Da and/or a length of between 1.5nm and about 5nm. The nanoparticle may have or comprise a ratio of electron acceptor species to electron donor species attached to the nanoparticle of between about 5 to 1 and about 13 to 1. The ratio of electron acceptor species to electron donor species may be between about 5 to 1 and about 12 to 1 , optionally between about 5.4 to 1 and about 11.7 to 1 , optionally about 5 to 1 and about 9.5 to 1 , and optionally between about 5.4 to 1 and about 9.2 to 1. It will be appreciated the specific parameters of the nanoparticle (such as nanoparticle size, linker length, electron donor species and/or redox potential, electron acceptor species and/or redox potential) may determine the parameters of the electric field (such as frequency, voltage, field strength etc.) required to drive electron transfer between the electron donor species and the electron acceptor species to modulate their redox states. According to a second aspect, there is provided the nanoparticle of the first aspect for use in modulating the biological activity or one or more cells. The method may be in vitro or in vivo. The cell may be a cancer cell, such as a cell derived from a glioblastoma , breast cancer, pancreatic cancer, oesophageal cancer or bile duct cancer. The biological activity may be apoptosis. According to a third aspect, there is provided the nanoparticle of the first aspect for use in medicine. According to a fourth aspect, there is provided the nanoparticle of the first aspect for use in treating cancer. The nanoparticle may be formulated in a pharmaceutical composition. According to a fifth aspect, there is provided use of the nanoparticle of the first aspect in the manufacture of a medicament for the treatment of cancer. The cancer may be glioblastoma, breast cancer, pancreatic cancer, oesophageal cancer, or bile duct cancer. According to a sixth aspect, there is provided a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amou nt of the nanoparticle of the first aspect. The method also comprises applying an electric field to the nanoparticle. The nanoparticle may be formulated in a pharmaceutical composition. The method may be in vitro or in vivo. The cancer may be glioblastoma, breast cancer, pancreatic cancer, oesophageal cancer or bile duct cancer. According to a seventh aspect, there is provided a method of modulating the redox state of the electron donor species and/or the electron acceptor species on the nanoparticle of any of the first aspect, second aspect, third aspect or fourth aspect. The method comprises applying an electric field to the nanoparticle. The method may be in vitro or in vivo. For the sixth and seventh aspects, the electric field may be an AC electric field. The electric field may have a frequency of between about 1 MHz and about 5 MHz, and optionally between about 1 MHz and about 3 MHz. Additionally, or alternatively, the electric field may have a strength of between about 0.6 V/cm and about 1.0 V/cm, optionally between about 0.6 V/cm and about 0.8 V/cm, and further optionally about 0.65 V/cm. The method may comprise applying the electric field using electrodes in contact with a medium (for example, cell culture media) containing the nanoparticle. The electric field may be applied for about 1 minute or more, about 5 minutes or more, about 10 minutes or more, about 30 minutes or more, about 60 minutes or more, 2 hours or more, 4 hours or more, 6 hours or more, 8 hours or more, 12 hours or more after each administration of the nanoparticle of composition of the invention. The electric field may be applied within one hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours of administration of the nanoparticles of the invention, In an eighth aspect, there is provided a pharmaceutical composition comprising the nanoparticle of the fist aspect. The nanoparticle for use, pharmaceutical composition, method of treatment, or one or more agent for use in the manufacture of a medicament according to the invention may be combined with other known therapies for the treatment of cancer. The skilled person will be able to identify a suitable known treatment for a given cancer and will understand that the known treatment for cancer will vary depending on the specifics of the cancer type and stage of the disease. In any nanoparticle for use, pharmaceutical composition, method of treatment, or one or more agent for use in the manufacture of a medicament according to the invention, the nanoparticle may be provided to a subject in need thereof. A subject may be any mammal, e.g., a human. Nonlimiting examples of non-human mammals include non-human primates, dogs, cats, mice, rats, guinea pigs, rabbits, fowl, pigs, horses, cows, goats, sheep, etc. The subject is preferably a human. The subject is preferably a human. In any aspect, the nanoparticle or composition of the invention may be administered with one or more further therapeutic. The one or more further therapeutic may comprise one or more of ciclosporin and mycophenolate. The nanoparticles or compositions of the invention may be delivered at intervals ranging from about 24 hours to about 2 days, to about 1 week, to about 2 weeks, to about 3 weeks to about 1 month to about 2 months, to about 3 months, to about 4 months, to about 5 months, to about 6 months. The scheduling of such dosage regimens can be optimized by the skilled physician. The nanoparticles or compositions of the invention may be administered using a treatment regimen comprising one or more doses, wherein the treatment regimen is administered over 2 days, 3 days, 4 days, 5 days, 6 days or 7 days, 14 days, 30 days or more. The nanoparticles or compositions of the invention may be administered daily, and an electric field, such as an alternating current at 3 MHz, 1.3 VPP, be applied for about 45 minutes after each administration. The precise dose to be employed in the formulations of the present invention may depend on the route of administration, and the seriousness of the condition, and should be decided according to the judgment of the practitioner and each patient's circumstances and can be determined by standard clinical techniques. Effective doses may be extrapolated from dose -response curves derived from in vitro or animal model test systems. The particular dosage regimen, i.e., dose, timing and repetition, will thus depend on the particular individual and that individual's medical history, as well as the route of administration. The agent or pharmaceutical composition may be administered to the subject indefinitely or for a specified period of time. The agent or pharmaceutical composition may be administered at regular intervals. As used herein, the term "therapeutically effective amount" refers to the total amount of the nanoparticle or each active component of the pharmaceutical composition or method that is sufficient to provide patient benefit, i.e., prevention or amelioration of the condition to be treated, a reduction in symptoms, an increase in rate of healing, or a detectable change in the levels of a substance in the treated or surrounding tissue. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in concurrently, sequentially or separately. A pharmaceutical composition of the invention may further comprise one or more carriers or excipients. For example, an excipient can give form or consistency, or act as a diluent. Suitable excipients include, but are not limited to, stabilizing agents, wetting and emulsifying agents, salts for varying osmolarity, encapsulating agents, buffers, and skin penetration enhancers. The compositions can be in any suitable form, for example tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders. Such compositions may be prepared by any known method, for example by admixing the active ingredient with the carrier(s) or excipient(s) under sterile conditions. Suitable formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form, for example, water-soluble salts. In addition, suspensions of the active compounds as appropriate for oily injection suspensions may be administered. Suitable lipophilic solvents or vehicles include fatty oils, for example, sesame oil, or synthetic fatty acid esters, for example, ethyl oleate or triglycerides. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension and include, for example, sodium carboxymethyl cellulose, sorbitol, and /or dextran. Optionally, the suspension may also contain stabilizers. Liposomes and/or nanoparticles can also be used to encapsulate the agent for delivery into the cell. A pharmaceutical formulation for systemic administration according to the invention may be formulated for enteral, parenteral or topical administration. Indeed, all three types of formulation may be used simultaneously to achieve systemic administration. Suitable formulations for oral administration include hard or soft gelatin capsules, pills, tablets, including coated tablets, elixirs, suspensions, syrups or inhalations and controlled release forms thereof. Generally, these agents are formulated for administration by injection (e.g., intraperitoneally, intravenously, subcutaneously, intramuscularly, etc.), although other forms of administration (e.g., oral, mucosal, etc.) can be also used. Preferably, these agents are formulated for administration by intravenous injection. Accordingly, agents of the invention are preferably combined with pharmaceutically acceptable vehicles such as saline, Ringer's solution, dextrose solution, and the like. Pharmaceutical compositions can also be formulated so as to provide quick, sustained or delayed release of their active ingredients after administration to the patient by employing procedures known in the art. The physical and chemical characteristics of the compositions of the invention may be modified or optimized according to the skill in the art, depending on the mode of administration and the particular disease or disorder to be treated. The compositions may be provided in unit dosage form, a sealed container, or as part of a kit, which may include instructions for use and/or a plurality of unit dosage forms. A variety of administration routes for the nanoparticles or pharmaceutical compositions of the invention are available. The particular mode selected will depend upon the particular nanoparticle or composition selected, the severity of the medical disorder being treated and dosage required for therapeutic efficacy. The methods of this invention may be practiced using any mode of administration that is medically acceptable, and produces effective levels of the active compounds without causing clinically unacceptable adverse effects. Such modes of administration include, but are not limited to, oral, buccal, sublingual, inhalation, mucosal, rectal, intranasal, topical, ocular, periocular, intraocular, transdermal, subcutaneous, intraarterial, intravenous, intramuscular, parenteral, or infusion methodologies. In a specific embodiment, it may be desirable to administer the pharmaceutical compositions of the invention locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion, by injection, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers. Features which are described in the context of separate aspects and embodiments of the invention may be used together and/or be interchangeable wherever possible. Similarly, where features are described in the context of a single embodiment for brevity, those features may also be provided separately or in any suitable sub-combination. Features described in connection with the nanoparticle of the first aspect may have corresponding features definable with respect to any of the second, third, fourth, fifth or sixth aspects, and vice versa, and these embodiments are specifically envisaged. |
| IP Reference | |
| Protection | Patent / Patent application |
| Year Protection Granted | 2024 |
| Licensed | No |
| Title | Team Bot app |
| Description | AZURE used to create a Bot App for teaching the research group bioelectronics |
| Type Of Technology | Webtool/Application |
| Year Produced | 2021 |
| Impact | Increased understanding and this it's ownership has been transferred to University to trial as a teaching aid. |
| Description | Asilomar Bioelectronics Symposium, Pacific Grove, CA, USA (2019) - Awarded best poster presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Combination of mechanical and electrical cues to develop novel bioelectronic micro-scaffolds, Paola Sanjuan-Alberte, Jayasheelan Vaithilingam, Chris Denning, Richard JM Hague, Morgan R Alexander, Frankie J Rawson. Asilomar Bioelectronics Symposium, Pacific Grove, CA, USA (2019) - Awarded best poster presentation |
| Year(s) Of Engagement Activity | 2019 |
| Description | Electrochem talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | A talk on Tracking ultrashort carbon nanotubes in NG108 neurons was given |
| Year(s) Of Engagement Activity | 2019 |
| Description | MRS interview |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview for MRS bulletin which was published as a blog/podcast |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://mrsbulletin.buzzsprout.com/244633/2310434-episode-24-gold-nanoparticles-modify-electrical-be... |
| Description | Modulating Bioelectricity in cancer towards quantum theapeutics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | A talk to the Quantum Biology Centre at the University of Surrey |
| Year(s) Of Engagement Activity | 2022 |
| Description | Modulating Bioelectricity in cancer towards quantum theapeutics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | A talk to the Quantum Biology Centre at the University of Surrey |
| Year(s) Of Engagement Activity | 2022 |
| Description | Presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Tracking ultrashort carbon nanotubes in NG108 neurons at the Gordon Conference on bioelectonics |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentations: Novel strategies to remotely control bioelectronic systems. RSC 6th Analytical Biosciences Early Career Researcher Meeting. Cambridge, UK, 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Presentations: Novel strategies to remotely control bioelectronic systems. RSC 6th Analytical Biosciences Early Career Researcher Meeting. Cambridge, UK, 2019 |
| Year(s) Of Engagement Activity | 2019 |
