The development of mass spectrometric analytical methods for the determination of the biological fate of lipid-based drug delivery nanoparticles

测定脂质药物递送纳米颗粒生物命运的质谱分析方法的发展

• 批准号: 382878-2010
• 负责人: ElAneed, Anas
• 金额: $ 2.55万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=550232
• 关键词: development; mass; spectrometric; analytical; methods

The proposed research program aims at determining the fate of cationic-lipid based nanoparticles within cell tissue cultures, utilizing state-of-the-art mass spectrometric techniques. Cationic lipid nanoparticles have demonstrated a great potential as gene delivery systems. However, it is not fully understood what happens to the delivery system once the gene is delivered to the targeted tissue/cell. My research program can address this essential gap in knowledge. Different cationic lipids have varying toxicological profiles in cell cultures as changes in the chemical structure of the cationic lipids has modified the cell viability profile (i.e. toxicity) upon exposure. In this program, I am evaluating the fate of two structurally related cationic lipid groups, namely diquaternary ammonium gemini surfactants (that include 2 different structural subfamilies) and novel gemini pyridinium surfactants. These compounds are chosen because they have shown promise as gene delivery systems and exhibit different toxic profiles within cultured cells. Variation in toxicity, based on chemical modifications, was also observed within each group. The proposed research will monitor the fate of the tested cationic lipids including subcellular localization and metabolite formation. Their behavior within cells may explain the variation in the toxic profiles among different cationic lipids. The long term goal of my research program is to enhance our understanding of the interactions between the chemical structure of cationic lipids and biological systems (i.e. tissue cultures). The knowledge produced will be used in engineering new lipid materials that are non-toxic and efficient in gene delivery.

拟议的研究计划旨在确定细胞组织培养物中阳离子基于阳离子脂质的纳米颗粒的命运，利用最先进的质谱技术。 作为基因递送系统，阳离子脂质纳米颗粒具有巨大的潜力。 但是，一旦将基因传递到靶向组织/细胞，尚未完全了解递送系统会发生什么。 我的研究计划可以解决知识的这一基本差距。 随着阳离子脂质的化学结构的变化，不同的阳离子脂质在细胞培养物中具有不同的毒理学特征，在暴露后改变了细胞活力（即毒性）。 在该程序中，我评估了两个与结构相关的阳离子脂质基的命运，即双含铵双子表面活性剂（包括2种不同的结构亚家族）和新型的双子吡啶表面活性剂。之所以选择这些化合物，是因为它们已显示为基因递送系统的希望，并在培养的细胞中表现出不同的有毒谱。基于化学修饰的毒性变化也观察到每组中。 拟议的研究将监测经过测试的阳离子脂质的命运，包括亚细胞定位和代谢产物形成。 它们在细胞中的行为可能解释了不同阳离子脂质之间毒性谱的变化。我的研究计划的长期目标是增强我们对阳离子脂质和生物系统化学结构（即组织培养物）之间相互作用的理解。 产生的知识将用于工程新的脂质材料，这些脂质材料在基因递送方面具有无毒和有效。