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  Determining the biocompatibility of, novel, nano-silica coated surfaces on oral and gastrointestinal immune barriers


   Department of Pharmacology and Therapeutics

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The interaction of nanoparticles with cells, particularly those that are immune-competent, may affect their biocompatibility, particularly when applied in long-term situations. Assessment of the biocompatibility of any new material is vital to its successful translation.

It is well known that surface topography can influence cellular interactions with surfaces. We have demonstrated that nanoparticulate silica can be bound to surfaces via a polycationic polymer binder to form a random close-packed monolayer. The silica is amorphous nanoparticles in the range of 7-21nm which are negatively charged and have a very low solubility. When we add a low-concentration solution of a cationic polymer (charge head group and hydrophobic tail) it binds to the nanoparticle surface and owing to its hydrophobic tail will clump into small patches on the surface. This produces a stable colloidal solution of silica nanoparticles which when exposed to a hydrophobic surface facilitates attachment to the surface via the hydrophobic polymer patches. We have shown that these modified surfaces significantly reduce the attachment of mammalian cells and fungal spores. Furthermore, those cells that do attach do not proliferate or, in the case of Candida albicans, do not differentiate into their pathological form. These materials have a number of applications around the oral mucosa.

Exposure of cells at the oral mucosa, to novel materials, necessitates investigation of possible issues around the biocompatibility of these materials. Nano-silica is known to be proinflammatory, primarily through its recognition by the NLRP3 inflammasome complex. Activation of NLRP3 leads to the activation of immune cells and release of proinflammatory mediators as well as potentially pyrogenic cell death (pyroptosis) which may, in turn, cause the bystander activation of sentinel immune cells. The aim of this project would be to determine the biocompatibility of these nano-silica coated surfaces to determine if the spatial orientation of the nano-silica causes NLRP3 activation when compared to non-tethered nano-silica. Primarily, this will be accomplished using a co-culture model which represents the oral mucosa and the gingival crevice, in particular. The latter is a barrier that is constantly exposed to environmental stimulation by the tooth microbiome and the tissue damage that arises from chewing and hygiene regimens. Studies have revealed an accumulation of inflammatory cells at steady-state in the gingiva and at higher levels than in other sites of the oral mucosa. This project will determine if these cells have a higher tolerance for activation, compared to cells of the gastrointestinal tract, which may be exposed to nano-silica not bound to the tethering surface.

This, multidisciplinary, project will provide training in the development of novel nano(bio)materials, and modern immunological and cell biology techniques as well as afford the opportunity to develop, and refine, novel in vitro models of the oral and intestinal mucosa.


Biological Sciences (4) Engineering (12) Medicine (26)

Funding Notes

This project is, currently, only open to self-funded students.

References

David, C. A. W., M. Barrow, P. Murray, M. J. Rosseinsky, A. Owen and N. J. Liptrott (2020). "In Vitro Determination of the Immunogenic Impact of Nanomaterials on Primary Peripheral Blood Mononuclear Cells." Int J Mol Sci 21(16).
David, C. A. W., M. E. Del Castillo Busto, S. Cuello-Nunez, H. Goenaga-Infante, M. Barrow, D. G. Fernig, P. Murray, M. J. Rosseinsky, A. Owen and N. J. Liptrott (2021). "Assessment of changes in autophagic vesicles in human immune cell lines exposed to nano particles." Cell Biosci 11(1): 133.
Halamoda-Kenzaoui, B., R. J. Vandebriel, A. Howarth, M. Siccardi, C. A. W. David, N. J. Liptrott, M. Santin, S. E. Borgos, S. Bremer-Hoffmann and F. Caputo (2021). "Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation." J Control Release 336: 192-206.
Hobson, J. J., S. P. Rannard, A. Owen and N. J. Liptrott (2020). "Safety assessment of a new nanoemulsion-based drug-delivery system reveals unexpected drug-free anticoagulant activity." Nanomedicine (Lond) 15(14): 1361-1373.
Vandebriel, R. J., C. A. W. David, J. P. Vermeulen and N. J. Liptrott (2022). "An inter-laboratory comparison of an NLRP3 inflammasome activation assay and dendritic cell maturation assay using a nanostructured lipid carrier and a polymeric nanomedicine, as exemplars." Drug Deliv Transl Res 12(9): 2225-2242.

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