Vaccine delivery: Characterization of vaccine delivery and metabolic impact investigation using secondary ion mass spectroscopy

使用负载的纳米颗粒来表达预防性抗原和治疗性蛋白质已经在医疗保健中启动了新一代的生物技术，其使用非病毒递送载体来安全且有效地递送外源性遗传有效载荷（例如，以对抗人畜共患病来源的传染病）。疫苗的有效递送必须克服一系列生理和生物屏障，目前我们对这些屏障的理解有限。该项目旨在使用最先进的表征技术（如质谱成像）来解决这些限制。合成纳米颗粒是具有非内源性存在于细胞中的独特组分的递送载体。这些组分将用于跟踪递送载体，并在使用诸如二次离子质谱法的表征技术时为纳米颗粒提供化学“指纹”。这将用于本项目，以提高我们的能力，询问生理环境的映射的化学指纹的传递媒介和外源性疫苗机制的代谢影响。与GSK密切合作，该项目取得的成果将提供关键的机制证据，通过提供有关如何交付和影响细胞环境的见解来改进疫苗和交付载体的设计。

The use of loaded nanoparticles to express prophylactic antigens and therapeutic proteins has initiated a new generation of biotechnology in healthcare using non-viral delivery vehicles to safely and potently deliver the exogenous genetic payloads (e.g. to combat infectious diseases of a zoonotic origin). Effective delivery of vaccines must negotiate a series of physiological and biological barriers for which our understanding is presently limited. This project aspires to address these limitations using state of the art characterisation techniques such as mass spectrometry imaging. Synthetic nanoparticles are delivery vehicles that have unique components that are not endogenously present in cells. These components will be used to follow the delivery vehicle and provide a chemical "fingerprint" for the nanoparticle when using characterization techniques such as secondary ion mass spectrometry. This will be used in this project to improve our capacity to interrogate the physiological environments by mapping the chemical fingerprint of the delivery vehicle and metabolic impact of exogenous vaccine mechanisms. Working closely with GSK, the results achieved in this project will provide key mechanistic evidence to improve the design of vaccine and delivery vehicles by providing insight regarding how delivery occurs and influences the cellular environment.