Nanoplexes for biological therapies

在生物治疗领域中，需要有效的“药物递送系统”来满足“生物衍生的”药物递送的规格。生物治疗，我。使用非病毒载体将核酸（DNA、RNA）、蛋白质和肽递送至细胞，以及将细胞递送至目的部位，是有效治疗许多遗传和慢性疾病的有希望的途径。用于生物治疗的传统生物材料基本上是从常规药物递送系统“借用”的。尽管各种微/纳米颗粒载体系统的发展，生物治疗的最终结果仍然温和。这是由于对载体系统的细胞摄取和细胞内运输的基本机制理解不足。通过我们的工作，我们采用组合方法将新功能引入纳米载体系统，以改善其结构多样性以及与细胞和生物分子的相互作用。我们在“生物衍生”药物的控制递送领域的研究的总体目标是开发具有靶向和跟踪能力的多功能纳米复合物，以克服生物疗法的局限性，检查递送载体及其细胞货物的内化过程和命运。更具体地说，我们建议开发基于壳聚糖衍生物的多功能基因递送载体，用于血管修复和动脉粥样硬化的治疗。提出了三种办法：1）用于将遗传物质递送至内皮细胞以进行相关成像的光不稳定纳米复合物; 2）靶向内皮祖细胞的核-壳E3纳米颗粒递送系统;和3）促进内皮祖细胞分化为成熟内皮的多功能纳米复合物基因抑制系统。根据Can。J. Cardiology（2010年10月，26（8）：e297-e305），心血管疾病占加拿大死亡人数的30%。加拿大人与动脉粥样硬化血栓形成相关的经济负担，包括医生服务、住院、工资损失和生产力下降，每年总计222亿美元。我们在这项研究中的成功可以为加拿大和全球的医疗保健系统提供即时救济。

Potent "drug delivery systems" are required to meet the specifications of "biologically-derived" drug delivery in the field of biological therapy. Biological therapy, i. e the delivery of nucleic acids (DNAs, RNAs), protein and peptides to the cell using non-viral vehicles, as well as cells delivery to the site of interest, are promising avenues for effective treatment of many genetic and chronic diseases. Traditional biomaterials for biological therapy are essentially "borrowed" from conventional drug delivery systems. Despite the development of various micro/nano particulate carrier systems, the final outcomes of biological therapy remain modest. This is attributed to poor understanding of the underlying mechanisms governing cellular uptake and intracellular trafficking of carrier systems. Through our work, we employ combinatorial approaches to introduce new features into nanocarrier systems to improve their structural diversity and interactions with cells and biological molecules. The overall aim of our research in the field of controlled delivery of "biologically-derived" drugs is to develop multifunctional nanoplexes possessing both targeting and tracking capabilities to overcome limitations of biological therapies, examining the internalisation process and fate of the delivery vehicle and its cellular cargo. More specifically, we propose to develop multifunctional gene delivery vehicles based on chitosan derivatives for use in vascular repair and treatment of atherosclerosis. Three approaches are proposed: 1) Photo-labile nanoplexes for delivery of genetic materials to endothelial cells for correlative imaging; 2) Core-shell Estradiol nanoparticle delivery systems targeting endothelial progenitor cells; and 3) Multifunctional nanoplex gene inhibitory systems promoting endothelial progenitor cell differentiation to mature endothelium. According to the Can. J. Cardiology (October 2010, 26(8):e297-e305), cardiovascular diseases account for 30% of deaths in Canada. The economic burden associated with atherothrombosis for Canadians, including physician services, hospitalizations, lost wages and decreased productivity, totals $22.2 billion annually. Our success in this research could provide instant relief to health care systems both within Canada and globally.