High-throughput quantification of drug loading into advanced delivery systems at the single particle scale

影响骨骼系统的疾病可能特别难以治疗。为了增强药物靶向，已经尝试设计合成的基于脂质的纳米颗粒药物递送系统（DDS，例如脂质体）。在过去的25年中，通过改变脂质成分或通过连接组织靶向配体（如抗体）来工程化纳米颗粒表面，已经取得了进展。尽管如此，生物分布研究表明，大多数这些颗粒在肝脏中蓄积（<70%），在临床靶点中观察到的最大摄取量为0.7%。我们的身体已经进化出了有针对性的生物材料交换的自然网络。这些复杂的纳米颗粒载体，称为细胞外囊泡，自然适应于避免免疫系统的清除，并穿越复杂的生物屏障，阻止高达98%的小分子药物通过。因此，EV为先进的药物递送提供了一种新的生物相容性替代方案，在目前难以甚至不可能到达的部位提供了增强的选择性。尽管EV技术提供了优势，但由于缺乏能够准确定量载药效率和定位的高通量分析方法，利用这些颗粒递送治疗性货物的尝试受到限制。这个跨学科的项目将适应和优化最先进的纳米流式细胞仪平台（NanoFCM），以开发未来的高通量技术，能够在纳米尺度上量化药物负载。

Diseases that affect the skeletal system can be particularly difficult to treat. To enhance drug targeting, attempts have been made to engineer synthetic lipid-based nanoparticle drug delivery systems (DDS, e.g. liposomes). Over the last 25 years, advancements have occurred by varying lipid composition or by engineering the nanoparticle surface through the attachment of tissue-targeting ligands such as antibodies. Nonetheless, biodistribution studies have shown that most of these particles accumulate in the liver (<70%) with a maximum of 0.7% uptake observed in clinical targets. Our bodies have evolved natural networks for the targeted exchange of biological materials. These sophisticated nanoparticle carriers, termed extracellular vesicles, are naturally adapted to avoid clearance by the immune system and traverse complex biological barriers that prohibit the crossing of up to 98% of small molecule drugs. As such, EVs offer a novel and biocompatible alternative for advanced drug delivery that provide enhanced selectivity at sites that are currently difficult or even impossible to reach. Despite the advantages offered by EV technologies, attempts to exploit these particles for the delivery of therapeutic cargos are limited due to a lack of high-throughput analytical methods capable of accurately quantifying drug loading efficiency and localisation. This interdisciplinary project will adapt and optimise a state-of-the-art nano-flow cytometry platform (NanoFCM) to develop a future high-throughput technique capable of quantifying drug loading at the nano-scale.