Q-starch based, cargo dependent intracellular targeted delivery system

Different therapeutic molecules such as proteins, DNA and RNA needs to operate at different target site in the cells. The difficulty in reaching these target sites is mainly due to the extracellular and intracellular barriers such as electrostatic repulsion of the cell membrane, endosomal escape, and the nuclear envelope. To overcome these barriers a biocompatible, biodegradable, and non-toxic carrier which can attach the cargo, therapeutic molecule, is required. Modified starch-based delivery system with a positively charge group (Q-starch) allows binding of negatively charged molecules to create a complex with suitable size and charge enabling overcoming the cellular uptake obstacles. The hypothesis in this study was that Q-starch is a suitable carrier for different therapeutic molecules such as pDNA, siRNA and Phosphatidylinositol-3,4,5-trisphosphate (PIP3), and can carry them to the desired target site while maintaining their biological activity. pDNA, siRNA and PIP3 have therapeutic biological activity at different sites in the cell: nucleus, cytoplasm, and cell’s membrane respectively. Q-starch complexes with pDNA, siRNA and PIP3 were evaluated by dynamic light scattering, zeta potential, and Cryo-TEM presenting formation of spherical, nano-sized, positively charged complexes. These three complexes examined in this work presented cellular uptake corresponding to the site where the therapeutic molecules are active in their natural state. In addition, the biological activity of the cargo for each target site was observed. We therefore conclude that the Q-starch/cargo complexes target site is cargo dependent.