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Targeted drug delivery via specific cellular receptors has been realized as a crucial strategy for successful therapy by maximizing therapeutic efficiency on target cells and minimizing systemic side-effects. Prof. Hashida and Lecturer Kawakami have developed glycosylated (galactose, mannose, fucose, and mannose-6-phosphate modified) liposomes for cell-selective targeting of plasmid DNA and siRNA and demonstrated their therapeutic activities against various disease models. Recently, the researchers have developed a new gene delivery system in which glycosylated bubble lipoplexes are combined with ultrasound (US) exposure. Intravenous injection of mannosylated bubble lipoplexes followed by US exposure resulted in specific delivery of plasmid DNA (pDNA) and siRNA to splenic dendritic cells or hepatic endothelial cells (HECs) expressing a mannose receptor in mice. DNA vaccine with pDNA expressing ovalbumin (OVA) or melanoma-related antigen (gp100) as a model antigen exhibited high growth inhibition activities against solid and metastatic tumors. The siRNA against intracellular adhesion molecule-1 (ICAM-1) administered with this system exhibited strong reduction of inflammatory responses by knocking out of ICAM-1 production in HECs and suppressed migration of neutrophil. Thus, the novel gene delivery system with mannosylated bubble lipoplexes administration and US exposure demonstrated specific and efficient nucleic acids delivery and therapeutic efficacy.



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