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Dial-a-membrane: precision engineering of sub-micron self-assembled materials

Lead Research Organisation: Imperial College London
Department Name: Chemical Engineering

Abstract

Liposomes and related amphiphilic assemblies have received much interest in recent years due to their wide biotechnological potential. This ranges from their use as capsules for targeted drug and vaccine delivery, miniaturised bioreactors, biosensors, tools for pharmacokinetic screens, and as cell models for the study of fundamental biology. They are increasingly being functionalised with biological machinery, which has led to them being exploited as the base motif for artificial cells: structures that mimic biological cells in form/function, which can perform user-defined tasks as biomimetic microdevices.

Liposomes used in these applications share a common structure, namely that of a spherical compartment encased by a lipid bilayer. This lack of architectural diversity has hindered their technological potential. However, we know from biology that step changes in the sophistication of chemical microsystems can be achieved by having non-uniform spatial organisation; this is achieved through compartmentalisation of content in discrete spatial locations.

In this project, we will develop new platform technologies which will enable a host of compartmentalised nanostructures that can be made-to-order, with full control over all relevant parameters including size, compartment number, and composition/phase state of individual compartments and their associated membranes. Once established, this new paradigm has the potential to underpin a host of applications in biotechnology, and provide new insights on fundamental biology through the use of biomimetic models that cannot yet be replicated in-vitro despite being pivotal to life. We will exploit the control afforded by this approach to create stimuli-responsive particles for in-situ drug synthesis as well as multi-stage therapeutic payload release, paving the way for industrial and clinical applications.

Publications

10 25 50
 
Description In this project, we successfully developed new microfluidic technologies to create novel self-assembled nanoparticles with exceptional control over their size, shape, structure, and composition. These include multi-compartment nanoparticles capable of releasing different payloads at specific times in response to external stimuli. This has the potential to underpin multi-stage delivery, as well as co-delivery of different cargos, leading to more effective therapeutics.
We also used these technologies to trigger chemical reactions inside the nanoparticles, effectively turning them into atto-litre reaction chambers. This could enable targeted synthesis of drugs or other molecules exactly where they are needed (synthesis at the sie of action) followed by controlled release.
Additionally, we created other types of advanced nanoparticles, including microgels, hexosomes, and cubosomes. Our research showed that particle size plays a crucial role in how well they deliver their payloads to cells-smaller particles fused with cells more effectively, while larger ones did not. This insight is critical for designing the next generation of drug delivery systems, which we are now further developing in follow-up projects.
Exploitation Route Our findings and technologies are being applied-both by our team and by others-in collaboration with biomedical scientists and clinicians to develop more effective therapeutics. Our devices are publicly available, and researchers worldwide, including in China, Japan, and the USA, are using our designs in their projects. Additionally, our fundamental insights into the biophysics of nanoparticle delivery-particularly the role of particle size in fusion with synthetic cell membranes-provide valuable scientific knowledge. These findings support the rational design of more effective drug delivery systems.
Sectors Chemicals

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

 
Description Adventurous Manufacturing Follow On: Integrating Living Analytics into Biomanufacturing Processes
Amount £870,445 (GBP)
Funding ID EP/W00979X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2022 
End 02/2025
 
Description BBSRC-NSF/BIO - Deciphering the rules of nucleus architecture with synthetic cells and organelles
Amount £601,388 (GBP)
Funding ID BB/W00125X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2022 
End 08/2025
 
Description Commercial exploitation of BioHydbrids for bacterial cell therapies 
Organisation Neobe Therapeutics Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are partnering with this company directly, through a PhD student who will spend time in both our labs. We will be providing our expertise and technology for BioHydbrid assembly developed during this award
Collaborator Contribution Our partners will be proving their expertise and cellular technologies for bacterial cell therapies
Impact This collaboration has only recently begun, no outputs yet
Start Year 2023
 
Description Commercial exploitation of BioHydbrids for bacterial cell therapies 
Organisation Neobe Therapeutics Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are partnering with this company directly, through a PhD student who will spend time in both our labs. We will be providing our expertise and technology for BioHydbrid assembly developed during this award
Collaborator Contribution Our partners will be proving their expertise and cellular technologies for bacterial cell therapies
Impact This collaboration has only recently begun, no outputs yet
Start Year 2023
 
Description Establishment of the fabriCELL centre for artificial cell science 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have founded the fabriCELL centre for artificial cell science, bringing together >40 academics groups in the UK to explore the development of artificial cell technologies in industry, biomedicine, and fundamental science applications. We co-Founded the initiative, and are co-Directors.
Collaborator Contribution Our partners from elsewhere at Imperial and other Universities (Kings College, Oxford, Cambridge ) feed into achieving the scientific and societal aims of the centre.
Impact We have organised a Royal Society discussion series on Artificial Cells. 400 attendees expected, from academia and industry. We are hosting brainstorming sessions and ideation events to foster grant applications and flexible engagement with industry. We are hosting outreach events, and engaging with members of the public through social media and online videos
Start Year 2021