Rationalising drug delivery using nanoparticles : a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles
Connell, David J. and Gebril, Ayman and Khan, Mohammad A. H. and Patwardhan, Siddharth V. and Kubiak-Ossowska, Karina and Ferro, Valerie A. and Mulheran, Paul A. (2018) Rationalising drug delivery using nanoparticles : a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles. Scientific Reports, 8. 17115. ISSN 2045-2322 (https://doi.org/10.1038/s41598-018-35143-7)
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Abstract
Silica nanoparticles (SiNPs) have been shown to have significant potential for drug delivery and as adjuvants for vaccines. We have simulated the adsorption of GnRH-I (gonadotrophin releasing hormone 1) and a cysteine-tagged modification (cys-GnRH-I) to model silica surfaces, as well as its conjugation to the widely-used carrier protein bovine serum albumin (BSA). Our subsequent immunological studies revealed no significant antibody production was caused by the peptide-SiNP systems, indicating that the treatment was not effective. However, the testosterone response with the native peptide-SiNPs indicated a drug effect not found with cys-GnRH-I-SiNPs; this behaviour is explained by the specific orientation of the peptides at the silica surface found in the simulations. With the BSA systems, we found significant testosterone reduction, particularly for the BSA-native conjugates, and an antibody response that was notably higher with the SiNPs acting as an adjuvant; this behaviour again correlates well with the epitope presentation predicted by the simulations. The range of immunological and hormone response can therefore be interpreted and understood by the simulation results and the presentation of the peptides to solution, paving the way for the future rational design of drug delivery and vaccine systems guided by biomolecular simulation.
ORCID iDs
Connell, David J. ORCID: https://orcid.org/0000-0001-6951-8359, Gebril, Ayman, Khan, Mohammad A. H., Patwardhan, Siddharth V., Kubiak-Ossowska, Karina, Ferro, Valerie A. ORCID: https://orcid.org/0000-0003-1967-3603 and Mulheran, Paul A. ORCID: https://orcid.org/0000-0002-9469-8010;-
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Item type: Article ID code: 65905 Dates: DateEvent20 November 2018Published26 October 2018AcceptedSubjects: Medicine > Therapeutics. Pharmacology Department: Faculty of Engineering > Chemical and Process Engineering
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical SciencesDepositing user: Pure Administrator Date deposited: 31 Oct 2018 10:16 Last modified: 28 Sep 2024 13:58 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/65905