Stimuli-responsive nanoparticles for gene, drug delivery and nitric oxide delivery
Won Jong Kim
Associate Professor of Chemistry, Group Leader of Center for Self-assembly and Complexity, Institute for Basic Science (IBS)
Pohang University of Science and Technology (POSTECH)
April 14, 2016
Foege N130A, Wallace H. Coulter Seminar Room
For the synergistic gene therapy, gold nanoparticles were employed as photothermal agents or the templates for drug loading. The pH-responsive i-motif DNA was utilized for the effective intracellular performance of photothermal therapy and chemotherapy. The developed systems exhibited synergistic anticancer effects via combination of siRNA and photothermal/chemo therapy. In addition to gene delivery systems, self-assembled nanoparticles via multivalent host-guest chemistry between PTX and ?-cyclodextrin (?-CD) were reported as a novel paclitaxel (PTX) delivery platform. CD and PTX were polymerized into the pCD and pPTX which provide the chance to produce the stable inclusion complex in blood circulation and release drug in intracellular regions. Furthermore, we also developed novel nitric oxide (NO) delivery system using catecholamine and diazeniumdiolates. Simple two-step reactions comprising catecholamine and diazeniumdiolates enable virtually any material surfaces to release NO with appreciable storage.
In the case of photothermal gene therapy, the i-motif DNA formed interstrand tetraplex in endosomal acidic pH, which could induce the formation of Au nanoclusters, resulting in endosomal escape of AuNP clusters and release of siRNA in the cytosol. As a result, when irradiated with laser, the synergistic anticancer effects was established by combination of photothermal ablation and gene silencing. For the synergistic gene and chemotherapy, the pH-responsive i-motif DNA facilitated the disassembly of the gold nanoclusters and dehybridization of i-motif/RNAi duplex, resulting in the release of therapeutic antisense RNA and Dox. Therefore, drug-mediated apoptosis was significantly accelerated by sensitizing the cancer cells to the drug. For the PTX delivery, the nano-assembly showed the high stability in blood and intracellular esterase-responsive drug release properties owing to the strong multivalent host-guest interactions and the ester bond linkages. This well-designed polymeric nano-carrier demonstrated a long-term suppression of tumor growth in vivo. Finally, in the case of surface NO delivery, the developed methods could offer a versatile platform which could be applied to surfaces of various materials and resulting surfaces could efficiently inhibit
Prof. Won Jong Kim received his BSc from Hanyang University in 1998, and M.S. and Ph. D. in Biomolecular Engineering in 2004 at Tokyo Institute of Technology. During his graduate studies with Profs T. Akaike and A. Maruyama, he developed a polymer-mediated DNA detection system. From 2004 to 2007, he was a postdoctoral fellow at the University of Utah under the supervision of Prof. Sung Wan Kim. Currently, he is an associate professor at the Department of Chemistry, POSTECH and a group leader of Center for Self-assembly and Complexity, Institute for Basic Science (IBS). He received KCS-Wiley Young Chemist Award (2011), Wiley-PSK Journal of Polymer Science Young Scientist Award (2012), KCS-Award for the Advancement of Science (2014), and PSK-Mid-career Researcher Academy Award (2015).