Creation of nanomaterials capable of specific interaction with receptors, enzymes and nucleic acids and thereby manipulating the cellular signalling apparatus poses not only technological challenges but also conceptual ones, promising an exciting new paradigm of “supramolecular drugs”. Protein-protein interactions are central to most biological processes – from intercellular communication to programmed cell death – and represent a large and important class of targets for human therapeutics. The aim of our research is to explore the potential of molecularly imprinted nanoparticles (nanoMIPs) as new therapeutic entities capable of interacting specifically with extracellular and intracellular protein targets (receptors, enzymes and regulatory proteins), and to perform the role of “plastic” therapeutic antibodies, as candidates for enzyme and antibody replacement therapies.
Molecular imprinting of polymers represents the most generic, versatile, scalable and costeffective approach to the creation of synthetic molecular receptors to date. Three particular features have made MIPs the target of intense investigation:
- Their high affinity and selectivity, which are similar to those of natural receptors
- Their unique stability which is superior to that demonstrated by natural biomolecules
- The simplicity of their preparation and the ease of adaptation to different practical applications
Recent developments in the automated synthesis of nanoMIPs using an immobilised template approach, invented by our team, mean that for the first time a reliable supply of soluble synthetic nanoparticles with pre-determined molecular recognition and/or catalytic properties, sub-nanomolar affinities, defined size and surface chemistry can be made available for testing as potential bioactives.
In collaboration with our European partners we have used nanoMIPs successfully as a replacement for antibodies in ELISA-type assays, electrochemical and optical sensors. The commercialisation of this activity is spearheaded by University spin-out MIP Diagnostics. The exciting examples of our work with in vivo application potential are targeting membrane receptors, enzymes and quorum sensing molecules. We have also used nanoMIPs in life science to identify peptide epitopes for antibodies and membrane proteins. Very encouraging facts that enable practical applications of MIPs in vivo are a lack of polymer toxicity, ability of nanoMIPs to penetrate into cells and to cross the blood barrier.Recent developments in the automated synthesis of nanoMIPs using an immobilised template approach, invented by our team, mean that for the first time a reliable supply of soluble synthetic nanoparticles with pre-determined molecular recognition and/or catalytic properties, sub-nanomolar affinities, defined size and surface chemistry can be made available for testing as potential bioactives.
- Canfarotta F, et al. (2016) 'Biocompatibility and internalization of molecularly imprinted nanoparticles.' Nano Research vol. 9. Pp. 3463–347.
- Canfarotta F, et al. (2016) 'Solidphase synthesis of molecularly imprinted nanoparticles.' Nat Protoc, vol. 11. Pp. 443–455.
- Cecchini A, et al. (2017) 'Vivo Recognition of Human Vascular Endothelial Growth Factor by Molecularly Imprinted Polymers.' Nano Lett, vol. 17. Pp. 2307–2312.
Elena Piletska, Kal Karim, Antonio Guerreiro, Francesco Canfarotta, Katarzyna Smolinska, Joanna Czulak, Alvaro Garcia, Abeer Safaryan, Tom Bedwell, Mike Whitombe.