Rationalising drug delivery using nanoparticles: a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles

David J. Connell, Ayman Gebril, Mohammad A. H. Khan, Siddharth V. Patwardhan, Karina Kubiak-Ossowska, Valerie A. Ferro, Paul A. Mulheran

Research output: Contribution to journalArticle

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.
LanguageEnglish
Article number17115
Number of pages11
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 20 Nov 2018

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Immunology
Drug delivery
Gonadotropin-Releasing Hormone
Silicon Dioxide
Nanoparticles
Bovine Serum Albumin
Peptides
Testosterone
Vaccines
Antibodies
Cysteine
Epitopes
Carrier Proteins
Hormones
Adsorption

Keywords

  • silica nanoparticles
  • drug delivery
  • vaccines
  • antibody response

Cite this

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title = "Rationalising drug delivery using nanoparticles: a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles",
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.",
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Rationalising drug delivery using nanoparticles : a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles. / Connell, David J.; Gebril, Ayman; Khan, Mohammad A. H.; Patwardhan, Siddharth V. ; Kubiak-Ossowska, Karina; Ferro, Valerie A.; Mulheran, Paul A.

In: Scientific Reports, Vol. 8, 17115, 20.11.2018.

Research output: Contribution to journalArticle

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