Magnetite synthesis in biomimietic nanovesicles: innovative synthetic routes to tailored bio-nanomagnets

Lead Research Organisation: University of Leeds
Department Name: Physics and Astronomy

Abstract

Scientific and economic interest in nanotechnology has grown in recent years. Within this the quest to produce tiny and highly tailored magnetic particles, or nanomagnets is crucial. Nanomagnets have a range of practical uses. Historically they have been used for information storage such as tapes and hard drives. Recently this has expanded with the development of 3D information storage systems providing high density data storage. There is much interest in the medical applications of nanomagnets. Magnetic particles are being developed to provide targeted medicine within the body. For example, if drugs are tied to nanomagnets at the molecular level then they can be directed by a magnet to specific sites within the patient. This allows a drug to be delivered to a specific area, without harming the rest of the body. Similarly, nanomagnets can be used in hyperthermic therapies. This is where, after being directed to specific tumour sites, magnetic particles are heated to either destroy a tumour or activate a drug. Such particles also already have used as image enhancers for diagnostic medicine. However, as nanotechnology grows, so too does the need to develop precisely engineered nanomagnets. Different applications demand different shapes and sizes of particles and different magnetic properties. Producing nanomagnets with highly controlled; composition, size and shapes, in large enough amounts to be of use to these industries, has therefore become a key goal of researchers.Biomineralisation is the process that occurs in living organisms to produce minerals such as bones. Because genetics control biomineralisation processes the materials produced exhibit very precise, uniform and intricate formations down to the nanoscale. Magnetotactic bacteria biomineralise high quality uniform nanoparticles of the iron-oxide magnetite within biological shells (or vesicles) called magnetosomes, within the bacterial cell. Because magnetosomes exhibit considerable uniformity and precision they present a novel and attractive route to produce high quality nanoparticles.However, the biomineralisation method produces inefficient yields for commercial production and is also not very flexible, as the cell strictly controls morphology and composition, so the particles cannot be easily adapted (e.g. maximum cobalt doping 1.4%).In order to synthesise precision customised magnetic nanoparticles, we will explore a biomimetic approach where we take inspiration from nature to develop a nano-magnetite precipitation system within artificial magnetosome vesicles outside the cell. We will perform a simple ambient temperature chemical precipitation of magnetite within nano-vesicles to help control the particle size and incorporate biomineralisation proteins into the interior of the vesicles to further impose biologically precise morphology over the particles. The system will combine all the benefits of biomineralisation such as morphological precision and a biocompatible coating, with all the benefits of a chemical precipitation such as high yields and a more malleable system with respect to variation, so particles can be customised.Additionally this formation technique uses environmentally friendly conditions and the addition of a biocompatible lipid coating to the particles is also highly advantageous for healthcare applications.

Planned Impact

The research proposed will develop a biomimetic and flexible method of producing high yields of customised, highly uniform magnetic nanoparticles under ambient conditions for nanotechnological and biomedical applications. It can therefore be seen that the study proposed here has considerable long-term commercial implications, potentially benefiting industries producing nanomagnets for recording and information storage media, advanced electronics and healthcare nanotechnologies. By presenting a commercially viable route to high yields of precision particles this research could be further developed to make advanced technologies more cost efficient, thus more widely available, benefiting industries as well as governmental bodies such as the NHS and thus the general public with respect to quality of life. With this in mind I am currently pursuing a commercial exploitation strategy which will patent the successful method and to seek partnerships to exploit innovative industrial development of this biomimetic nanoparticle production. This is being done in consultation with the University of Leeds enterprise and innovations office and TechTran , and throughout the project further IP will be sought between UCL business and my collaborators all of whom have considerable expertise in research commercialisation and spin-out companies. Additionally, we will seek follow-on funding in the form of CASE and Industrial partnership awards. The project is inherently multidisciplinary and falls into 3 EPSRC signposted areas of Engineering-synthetic biology, Control of self-assembly and Nanoscience through engineering to application. The multidisciplinary nature of the project also provides excellent cross-disciplinary training for the PDRAs and the PhD student alike, additional to the excellent personal development training offered. Furthermore the project offers additional interdisciplinary networking and knowledge transfer, not only for the PDRAs and student, but also for the development of all the investigators and our groups. We plan to increase the impact of this project through a wide range of dissemination methods. We have a strong track-record in publishing results in the best high-profile journals and in gaining wide media coverage of our research to give maximum impact. We will follow a similar strategy for this project, disseminating our results promptly in the form of journal articles and conference papers, websites, while simultaneously working with the press office to gain media coverage. The skills and methodologies developed in the work will also be disseminated to students in the form of material in advanced undergraduate courses and project based laboratory skills training.

Publications

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Description Please note that this is the same grant and same work as EP/I032355/2 so the summary below will be identical in both entries. The funding for this project ended July 2016.
Scientific and economic interest in nanotechnology has grown. Within this the quest to produce tiny and highly tailored magnetic particles, or nanomagnets is crucial. Nanomagnets have a range of practical uses, recently expanded to medical applications such as targeted medicine within the body and/or hyperthermic therapies (where magnetic particles are heated to either destroy a tumour or activate a drug). Such particles also already have used as image enhancers for diagnostic medicine. However, as nanotechnology grows, so too does the need to develop precisely engineered nanomagnets. Different applications demand different shapes and sizes of particles and different magnetic properties. Producing nanomagnets with highly controlled; composition, size and shapes, in large enough amounts to be of use to these industries, has therefore become a key goal of researchers. This was the key objective of this project. This was to be achieved using a biomimetic approach. This is where we take inspiration from nature to engineering our own synthetic route. Im this case the inspiration is magnetic bacteria. These microorganisms biomineralise high quality uniform nanoparticles of the iron-oxide magnetite within biological shells (or vesicles) called magnetosomes, within the bacterial cell. Because magnetosomes exhibit considerable uniformity and precision they present a novel and attractive route to produce high quality nanoparticles. However, biomineralisation produces inefficient yields for commercial production and is also not flexible, as the cell strictly nanomagnets to be of the natural form. In this project we created artificial magnetosome vesicles and developed a nano-magnetite precipitation system within them were we mixed the reagents required to make magnetite by opening holes in the vesicles using an electric pulse to let the iron solution into the vesicle. This method has been very successful and has been published (Nature scientific reports 2015). This methodology can be expanded to a range of poylmersomes such as tribock (published in polymers 2015) and other functionalised polymersomes (paper in preparation). For liposomes we worked in collaboration with the UCL group to develop a high-yield, high-throughput production method using electrohydrodynamic atomisation. This was again successful, resulting in artificial magnetosomes with clear magnetite cores via a very promising scaleable route (published in Macromolecular Bioscience 2016). Remarkable we found we could tune the size, location and number of nanomagnets (from tiny 2-3nm sized in the membrane to larger 50 nm sized in the core of the vesicle) simply by altering the vesicle material, the reagent concentration and the electric field and pulse parameters (paper in preparation). Further to this, we have found that these different artificial magnetosomes give very different MRI and hyperthermic heating effects, so we can "tune" the magnetosomes to the biomedical applications. Finally work is ongoing to generate a biological artificial magnetosome using the native iron transporter proteins and biomineralisation proteins. This is the subject of a new grant proposal submitted to the BBSRC. Unfortunately this grant application was unsuccessful. However, a PhD student working across the disciplines, looking at magnetic nanoparticle uptake in cancer cells and using them for hyperthermic treatment has been using the methods developed in this grant to make better therapeutic nanoparticles. This is ongoing but will be good to see a real medical practical application of this work. Furthermore we have a masters student currently working on developing the artificial magnetosomes and by the summer we should have something to publish in this area.

Update from 2019. There is not sufficient work to publish the in vitro magnetosome work yet but will hopefully get the funding to put a summer student on this project. There is currently a master students working on the magnetospolymersomes with the PhD student. One paper in under review in this area and two are being written up.

Update 2020: The In vitro work has been discontinued as no summer student or fuinds to complete. The paper for the COOH funcrtionalised magentopolymerosme has been published with the remiining two still in the write up stage.
Exploitation Route All the magneto- nanovesicles are proving to be very promising candidates for nanomedicine (drug delivery, diagnostic and therapeutic delivery vehicles). We are collaborating with medics to realise the use of these nanomagnets for nanomedicine and have a joint PhD student working on this.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://bionanomagnetic.wordpress.com/
 
Description Matsunaga lab collaboration 
Organisation Tokyo University of Agriculture
Country Japan 
Sector Academic/University 
PI Contribution we collaborate academically with respect to magnetotactic bacteria
Collaborator Contribution we collaborate academically with respect to magnetotactic bacteria
Impact 5 research papers, I hosted a RS Newton fellow, we visit exchange students. etc.
Start Year 2006