Tailoring the atomic structure of advanced sol-gel materials for regenerative medicine through simulation

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

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Description While synthesising silica nanoparticles to valise theory and simulation studies of sol-gel silica, we found were able to synthesise silica nanoparticles that can deliver ionic zinc. Monodispersed zinc-containing mesoporous silica nanoparticles (MSNPs-Zn) were produced as a tuneable biodegradable platform for delivery of therapeutic zinc ions into cells. We demonstrate that the nanoparticles were internalised by cells and a therapeutic dose window was identified in which the MSNPs-Zn were toxic to breast cancer cells, but not to healthy epithelial (MCF-10a) cells or to murine macrophages. A significant reduction in the viability of triple negative MDA-MB-231 and MCF-7 (ER+) breast cancer cells was seen following 24 h exposure to MSNPs-Zn. The more aggressive MDA-MB-231 cells, with higher metastatic potential, were more sensitive to MSNPs-Zn than the MCF-7 cells. MSNPs-Zn underwent biodegradation inside the cells, becoming hollow structures, as imaged by high resolution transmission electron microscopy. The mesoporous silica nanoparticles provide a biodegradable vehicle for therapeutic ion release inside cells.
Exploitation Route Simulation of wet processes such as the sol-gel process are extremely challenging due to the limit of computing power. the methods developed here will enable others to carry out simulations on wet processes, especially sol-gel systems. The results generated for the sol-gel process will enable others to design new sol-gel compositions accurately.
The nanoparticles developed show that nanoparticles can deliver zin to cancer cells, killing them without killing other cells. this could be used to develop an alternative or complementary therapy to chemotherapy.
Sectors Education,Healthcare
 
Description Incorporation of other cations seem to be beneficial to cancer therapy. Tests with breast cancer cell lines and healthy endothelial cell lines showed a doseage window wherein the nanoparticles killed cancer cells but not their healthy equivalents. We have also incorporated nanoceria which adds synergistic antioxidant properties. We also developed nanoparticles with morphologies that can cross the blood brain barrier. This is the subject of a new research programme with the Francis Crick Institute, where they have a model of the blood brain barrier to test efficacy of the particles.
First Year Of Impact 2017
Sector Healthcare
 
Description Marie Curie Individual Fellowship
Amount € 200,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 06/2016 
End 05/2018
 
Description Bioactive nanoparticles 
Organisation Federal University of Minas Gerais
Country Brazil 
Sector Academic/University 
PI Contribution Hosting of Breno Rocha Barrioni. Methods for nanoparticle synthesis and role of nanoceria nanoparticles.
Collaborator Contribution Salary costs for Breno Rocha Barrioni
Impact New nanoparticles for therapeutic applications
Start Year 2017
 
Description Nanoparticles and the blood brain barrier 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have synthesised nanoparticles with new morphologies that can potentially safely cross the blood brain barrier and deliver cargo to treat conditions such as tuberculosis meningitis and dementia
Collaborator Contribution Professor Robert Wilkinson has devised an in vitro blood brain barrier model. The team are testing the cellular response to our nanoparticles
Impact A grant application to UKRI
Start Year 2020