Nanoplexes for biological therapies

在生物治疗领域，需要强有力的“药物输送系统”来满足“生物衍生”药物输送的要求。生物治疗，即使用非病毒载体将核酸(DNA、RNA)、蛋白质和多肽运送到细胞，以及将细胞运送到感兴趣的部位，是有效治疗许多遗传和慢性疾病的有效途径。用于生物治疗的传统生物材料基本上是从传统的药物输送系统中“借来”的。尽管各种微/纳米颗粒载体系统得到了发展，但生物治疗的最终结果仍然有限。这归因于对控制细胞摄取和细胞内载体系统运输的潜在机制的了解不足。通过我们的工作，我们使用组合方法将新的特征引入纳米载体系统，以改善它们的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”药物受控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网络，以克服生物疗法的限制，研究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。提出了三种途径：1)光不稳定的纳米复合体，用于将遗传物质输送到内皮细胞进行相关成像；2)以内皮祖细胞为靶点的核-壳雌二醇纳米颗粒输送系统；3)多功能纳米复合体基因抑制系统，促进内皮祖细胞向成熟内皮分化。据罐头说。J.心脏病学(2010年10月26日(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相关的经济负担，包括医生服务、住院、工资损失和生产率下降，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的缓解。

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.