Department of Chemical and Process Engineering, University of Strathclyde, 75 Montrose Street, Glasgow, G1 1XJ, UK.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Sci Rep. 2018 Nov 20;8(1):17115. doi: 10.1038/s41598-018-35143-7.
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 I) 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.
硅纳米颗粒（SiNPs）在药物输送和疫苗佐剂方面具有重要的潜在应用。我们模拟了 GnRH-I（促性腺激素释放激素 I）及其半胱氨酸标记修饰（cys-GnRH-I）在模型硅表面的吸附，以及其与广泛使用的载体蛋白牛血清白蛋白（BSA）的缀合。我们随后的免疫学研究表明，肽-SiNP 系统不会引起明显的抗体产生，表明该治疗无效。然而，与天然肽-SiNPs 相比，用原肽-SiNPs 处理后的睾酮反应表明存在药物作用，而用 cys-GnRH-I-SiNPs 处理则没有这种作用；这种行为可以通过模拟中发现的肽在硅表面的特定取向来解释。对于 BSA 系统，我们发现睾酮水平显著降低，特别是对于 BSA-天然缀合物，并且 SiNPs 作为佐剂的抗体反应明显更高；这种行为再次与模拟预测的表位呈现很好地相关。因此，通过模拟结果和肽在溶液中的呈现，可以解释和理解免疫和激素反应的范围，为基于生物分子模拟的药物输送和疫苗系统的未来合理设计铺平道路。
