Available: 03/01/20, Expires: 03/31/22
My research is focused on the development of novel targeted agents for cancer diagnosis, staging, and treatment. Using invisible near-infrared fluorescence imaging, my laboratory has systematically defined the chemical, optical, and physiological properties required for organic and inorganic contrast agents such as nanoparticles and fluorophores. Our long-term goal is to provide oncologic surgeons with useful and specific contrast agents for image-guided cancer surgery.
This important theme started when Nature Biotechnology published our article “Renal clearance of quantum dots” in 2007 (Choi et al., 25:1165). In that article, which has already been cited over 1,000 times, we hypothesized that ultrasmall and zwitterionic nanoparticles could target tumors efficiently while eliminating unbound material from the body via renal clearance. Indeed, we proved this hypothesis in the following papers Nat Nanotechnol. 2010;5:42 and Nat Biotechnol. 2013; 31:148.
Most recently, we developed target-specific NIR fluorophores using the concept of “structure-inherent targeting.” That is, a new, ultra-compact, bifunctional molecule with both high affinity binding to a target as well as NIR fluorescence, i.e., targeting and imaging. This strategy appears to work well, at least with the fluorinated polymethine (Hyun et al. Nat Med. 2015, in press) and phenoxazine model systems employed. Our approach from the phenotypic tissue level screening to the microscopic observation to find cellular level targets (organelle localization) is rather practical because it is based on in silico quantitative structure-affinity relationship (QSAR) design and in vivo feedback. Since this has been an excellent strategy that has served us productively, we will continue to use this approach to find out detailed cellular targeting mechanisms and to prepare the first-in-human clinical trials of selected agents in the current application.
Students will work closely with chemists, engineers, and surgeons to develop and optimize new targeted contrast agents. Their responsibilities in the laboratory will include design of novel near-infrared fluorophores and targeting drugs including synthesis, purification, characterization, and conjugation with biomolecules. Students will be trained with cancer cell culture, cell-based assay, and most importantly, the use of contrast agents in image-guided surgery using mice, rats, and pigs.