• Ministry of Science, ICT and Future Planning* together with the Institute for Basic Science** (IBS), the main organization of the International Science and Business Belt project in South Korea, have announced that a group of researchers led by Won Jong Kim succeeded in finding a scientific principle to intelligently deliver genes to a targeted site, while at the same time significantly improve therapeutic effects of anticancer treatments. Won Jong Kim is both a group leader for the Center for Self-assembly and Complexity*** at IBS and a professor at the Pohang University of Science and Technology (POSTECH).

* Minister, Mun-kee Choi ** Acting IBS president, Hee-Sup Shin *** Director, Kimoon Kim

• The researchers have discovered a scientific principle to develop DNA nanomachine-based nanostructures that can intelligently deliver genes responsive to the intracellular pH (potential of hydrogen), and can maximize the effect of near-infrared photothermal therapy used in anticancer treatments.

• By utilizing this principle, the diseased cells can be killed through a programmed release of genes to the specific diseased site, while simultaneously enhancing the effects of anticancer photothermal therapy. Thus, this new principle is expected to be applied in various medical fields, such as pharmaceuticals, healthcare and cancer treatments.

• The researchers have developed an intelligent DNA nanomachine that controls its motion according to the conditions present, while conjugating pH-responsive DNA (“i-motif DNA”) to the gold nanoparticles, and then hybridizes the small interfering RNA (“siRNA”), a therapeutic gene, to the i-motif DNA.

• Drawing from the idea that i-motif DNA has the ability to change its form and cluster together at low pH, the researchers hybridized i-motif DNA with the nucleic acid called siRNA which blocks the expression of target protein, and attached this formation on the surface of the gold nanoparticles.

• The researchers has found that the gold nanoparticles are dispersed while holding the siRNAs at the extracellular neutral pH until they enter into cells and then deliver the siRNAs by clustering together in response to the intracellular low pH. Furthermore, they found that the effects of anticancer treatments significantly improved by increasing photothermal ablation by way of clustering the gold nanoparticles.

• The anticancer therapies that use high temperatures produced by light (photothermal therapy) are expected to produce significant effects, if light-responsive gold nanoparticles are clustered together. If the gene therapy that destroys the diseased cells is conducted simultaneously, a synergistic effect can be achieved.

• The outcomes of this research were published online, June 10^th, in the prestigious nanoscience journal, issued by the American Chemical Society, ACS Nano (Impact factor of 12.062).

• Title of Paper: i-Motif-Driven Nanomachines in Programmed siRNA Delivery for Gene-Silencing and Photothermal Ablation

• First Author: Sejin Son, researcher for the Center for Self-assembly and Complexity at IBS

• Corresponding Author: Won Jong Kim, group leader for the Center for Self-assembly and Complexity at IBS

• “The development of an intelligent nanomachine that changes its motion according to the surrounding environment causes diseased cells, by gene, to die, and enhances the effects of photothermal therapy significantly when exposed to light. This is expected to improve the smart gene delivery system that can distribute the desired amount of genes at the proper time to a targeted site.” says Won Jong Kim, a group leader from the Center for Self-assembly and Complexity.