Cornell Dots: Multifunctional Nanomaterials for Enhancing Theranostics

Description:
This presentation describes a particular class of nanotheranostics, i.e. ultrasmall fluorescent core-shell silica nanoparticles referred to as Cornell dots (C dots). C dots have been successfully translated into multiple diagnostic as well as therapeutic clinical trials in oncology. Their ultrasmall size below the cut-off for renal clearance (particle diameters < 7-8 nm) leads to favorable biodistribution (BD) and pharmacokinetics (PK) profiles with high accumulation at the target site, low off-target accumulation, effective solid-tumor penetration, as well as efficient renal clearance (“target-or-clear”). The use of targeting moieties, including cyclic peptides as well as antibody fragments, increases targeting efficiencies over non-targeted analogues. Finally, surface modifications of the poly(ethylene glycol) (PEG) surface layer with therapeutic payloads that can be enzymatically cleaved when entering the target site, including small molecule inhibitors as well as chemotherapeutics, leads to unusually high drug loading capacities (>40 drug molecules per particle) without substantially effecting BD and PK profiles. This is enabled by the insertion of these typically more hydrophobic payloads in-between the hydrophilic PEG chains, keeping the overall particle surface characteristics PEG-like. As a result of very careful nanomaterials structure/composition versus biological response studies, including detailed gel permeation chromatography (GPC) and high-performance liquid chromatography (HPLC) particle characterizations enabled by the ultrasmall particle size, durable structure-biological property correlations are emerging providing blueprints for future nanomaterials applications in medicine. Furthermore, the recent discovery of “self-therapeutic” properties of such ultrasmall silica-based nanomaterials, i.e. anti-tumoral particle activities in the absence of cytotoxic payloads, opens exciting new opportunities for combinatorial treatment regiments.

Speaker: Ulrich Wiesner - Cornell University
Ulrich Wiesner studied Chemistry at the University of Mainz, Germany, and UC Irvine, CA. He gained his Ph.D. in 1991 in Physical Chemistry with work at the Max-Planck-Institute for Polymer Research (MPI-P), Mainz. After a postdoc at E.S.P.C.I. in Paris, France, he returned to the MPI-P in 1993. In 1998 he finished his Habilitation and received tenure as an MPI-P staff member. He joined the Cornell University, NY, Materials Science and Engineering (MSE) faculty in 1999 as a tenured Associate Professor, became a Full Professor in 2005, and since 2008 is the Spencer T. Olin Professor of Engineering. He holds secondary appointments in Chemical and Biomolecular Engineering (CBE), Biomedical Engineering (BME), and Chemistry and Chemical Biology (CCB). Since January of 2023 he is an inaugural faculty member of the Design Tech Department at Cornell and Professor of Design Tech. From 2015-2021 he was the co-director of one of six NCI funded Centers for Cancer Nanotechnology Excellence (CCNE).