Nanoplexes for biological therapies

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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.