Ting Xu

University of California Berkeley


Title: 

Rational Design of Nanocarrier for Cancer Treatment

Abstract:

~40% of the emerging small molecule drugs require drug formulations to improve their toxicity profile and efficacy. However, the physiological factors, including the density and heterogeneity of the vasculature at the tumor site and interstitial fluid pressure, impact the extent of extravasation of nanocarriers into tumors. Current FDA-approved Doxil (~100 nm) and Abraxane (~130 nm) have provided only modest survival benefits presumably due to inefficient transport of the chemotherapeutic drug into the tumor. Micelles, 10–30 nm in size, can cross different biological barriers and undergo deep tissue penetration and are ideal for nanocarriers and vaccine formulation. However, micelles in this size range have often shown limited in vivo stability, serious cargo leakage and rapid disassembly mainly due to their poor kinetic stability.

I am going to discuss our work in this area where directional entropic repulsion was used to manipulate the kinetic stability of nanocarriers under biological condition.  We developed family of sub-20 nm nanocarriers, called “3-Helix Micelle” (3HM) based on amphiphilic 3-helix peptide-PEG conjugate. 3HM has demonstrated long in vivo blood circulation halftime and renal clearance pathway. Using rats bearing glioblastoma (GBM), 3HM can readily across BBB through intravenous injection and deep penetrate into the tumor tissue. Quantitative structural and kinetic analysis suggest that the kinetic stability of 3HM was largely dictated by the combined effects of entropic repulsion associated with polymer chain conformation and the geometric packing of the subunit. The modular design approach coupled with mathematic model toward dosing design will significantly expand the translational potential to meet current demands in nanomedine.

Bio:

Dr. Ting Xu is the professor of Chemistry &Materials Science and Engineering at the University of California Berkeley and co-associate director of Precision Medicine and Healthcare Research Center at Tsinghua-Berkeley Shenzhen Institute. She and her research group work on the design, synthesis, and characterization of de novo designed peptides that serve as building blocks for functional biomaterials. They also seek to understand the hierarchical self-assembly of complex systems involving artificial proteins, block copolymers, and nanoparticles. She also focuses on a fundamental understanding of the physics of assemblageon multiple length scales leading to the design and assembly of functional thin films with tailored functionalities.