Core-Shell Nanoparticles for Enhanced, Synergistic, and Versatile Delivery of Nucleic Acid Therapeutics -- Speaker: Soo Kyung Cho, PH.D. Candidate, UCI
Gene therapy holds great promise for the treatment of inherited and acquired diseases by expressing therapeutic proteins or knocking out disease proteins. Even with immense potentials, delivery of nucleic acids into target cells is a major hurdle in gene therapy. Gene delivery vectors are largely divided into two major categories: viral and nonviral. Although they pose various disadvantages such as immunogenicity, pathogenicity, and native tropisms that are difficult to bypass, viruses have evolutionary advances in terms of tuning their properties to achieve efficient gene transfer. Therefore, it is not surprising for nonviral vectors to mimic viruses in order to develop efficient and safe gene delivery vectors. One key feature the majority of viruses have in common is their core-shell structure where nucleic acids are safely protected in the core and various functionalities are integrated in the shell to ensure efficient extracellular and intracellular trafficking.
In this talk, core-shell nano-systems prepared via surface-initiated photo-polymerization are discussed. This method allowed the preparation of various core-shell nano-systems with varying cores such as plasmid DNA (pDNA)/polyamine polyplexes, poly(amidoamine) dendrimers and even viruses (adeno-associated viruses). Cationic acid-degradable polyketal shell is designed to 1) protect cores during circulation, 2) enhance cellular uptake, 3) facilitate endosomal escape, 4) encapsulate secondary therapeutics such as siRNA for synergistic therapy, and 5) serve as platform for ligand conjugation. Synthesis, characterization, stimuli-responsive release, intracellular trafficking and in vitro efficiencies of various core-shell nano-systems are discussed as well as their efficacies in specific disease targets such as breast cancer and leukemia.
Soo Kyung Cho received a bachelor’s degree in Polymer Science and Engineering from Pusan National University (Korea) and master’s degree in Materials Science and Engineering from Seoul National University (Korea). Her master's thesis was on living radical polymerization of liquid crystalline polymers. Soo Kyung joined Prof. Young Jik Kwon's group as a Junior Specialist in 2008 and started her Ph.D. study in Medicinal Chemistry and Pharmacology gateway program in 2009 before she transferred to Materials Science and Engineering in 2010.