ChEMS Seminar: Design 15 nm Long-circulating Micelles as Viable Nanocarriers

Friday, May 1, 2015 - 3:00 p.m. to Saturday, May 2, 2015 - 3:55 p.m.
McDonnell Douglas Engineering Auditorium (MDEA)
Professor Ting Xu
Department of Materials Science and Engineering, Department of Chemistry
University of California, Berkeley

Nanocarriers, 10-30 nm in size, have unique advantages to improve therapeutic efficacy for drug delivery and vaccine formulation due to their ability to cross different biological barriers and undergo deep tissue penetration. However, micelles in this size range have limited in vivo stability, serious cargo leakage and rapid disassembly mainly due to their poor kinetic stability. We have developed 15 nm nanocarriers called “3-helix micelle” (3HM) based on amphiphilic peptide-PEG conjugates. The 3HM has a long blood circulation (t1/2 ≈ 29 hours), reasonable drug loading efficiency (8% with DOX) with minimal cargo leakage, selective accumulation of in tumors and reduced accumulation in the liver and the spleen. Using rats with U-87 MG xenograft, 3HM with PEGylated surface was shown to effectively and selectively localize within the GBM tumor tissue when administered through tail vein injection. The tumor region of interest (ROI) analysis (t-test, p=0.0060) showed that 3HM undergoes a significant increase in tumor accumulation from 3.5 hours to 21 hours post-injection, resulting in a final value of ~0.77%ID/cc in the ROI. This is significantly higher than liposomes (~0.45% ID/cc) used in the parallel experiment. I will report our recent studies to systematically understand the design principle to obtain micelles with tunable dynamic stability, controlled cargo release profile and multivalent ligand presentation.

Bio: Ting Xu received her Ph.D. from the Department of Polymer Science and Engineering from the University of Massachusetts, Amherst in 2004. She did her postdoctoral training jointly between the University of Pennsylvania and the Cold Neutron for Biology and Technology (CNBT) team at National Institute of Science and Technology from 2004-2006. She joined UC  Berkeley in both the Department of Material Sciences and Engineering and Department of Chemistry in January 2007. Researches in Xu's group take advantage of the recent developments in de novo protein design and peptidomimetics, polymer science and nanoparticles synthesis and manipulation; and use natural building blocks such as peptides and proteins in concert with the self-assembly of block copolymers, conjugated molecule and nanoparticles as platforms to generate nanostructured functional materials. Her research group focuses on a fundamental understanding of multiple length self-assemblies in multi-component systems and aims to generate hierarchically structured nanomaterials with built-in biological, electrical and magnetic functionalities. Xu has more than 60 peer-reviewed journal articles, five book chapters and several patents. She is the recipient of the 2007 DuPont Science and Technology Grant; 2008 3M Nontenured Faculty Award; 2008 DuPont Young Professor Award; 2009 Office of Naval Research Young Investigator Award; 2010 Li Ka Shing Woman Research Award; 2011 Camille-Dreyfus Scholar-Teacher Award; and 2011 ACS Arthur K. Doolittle Award. She was named as one of “Brilliant 10” by Popular Science Magazine in 2009.