Targeted nanoprobes for bioimaging and nanomedicine
Two fundamental and unsolved problems facing biophotonics and nanomedicine are nonspecific uptake of intravenously administered diagnostic and/or therapeutic agents by normal tissues and organs, and incomplete elimination of unbound targeted agents from the body. To solve these problems, we have synthesized a series of indocyanine near-infrared (NIR) fluorophores that varied systematically in net charge, conformational shape, hydrophilicity/lipophilicity, and charge distribution. Using 3D molecular modeling and optical fluorescence imaging, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting such as lung and sentinel lymph nodes (Nat Biotechnol. 2010), human prostate cancers (Nat Nanotechnol. 2010), and human melanomas (Nat Biotechnol. 2013).
Recently, we have developed new pharmacophore design strategy “structure-inherent targeting,” where tissue- and/or organ-specific targeting is engineered directly into the non-resonant structure of a NIR fluorophore, thus creating the most compact possible optical contrast agent for bioimaging and nanomedicine (Angew Chem. 2015, Nat Med. 2015). The biodistribution and targeting of these compounds vary with dependence on their unique physicochemical descriptors and cellular receptors, which permit 1) selective binding to the target tissue/organ, 2) visualization of the target specifically and selectively, and 3) provide curing options such as image-guided surgery or photo dynamic therapy. Our study solves two fundamental problems associated with fluorescence image-guided surgery and lays the foundation for additional targeted agents with optimal optical and in vivo performance.
Hak Soo Choi, PhD, is a leader in the field of nanotechnology and nanomedicine and the Principal Investigator of the Choi Laboratory. His laboratory focuses on the development of novel disease-specific contrast agents for diagnosing, staging, and treating cancer. His special areas of interest are targeted nanoparticles, which are capable of carrying large diagnostic and treatment agents to a specific tissue, and the discovery of compounds that bind specifically to living cancer cells. Dr. Choi supervises the Robotic Chemistry Group at the Center for Molecular Imaging. The Robotic Chemistry Group has developed a system of technology that is capable of quickly screening thousands of small molecules against dozens of types of living cancer cells. He has published over 47 peer-reviewed original articles, 16 proceedings, and 60 abstracts. He is the recipient of several awards and honors, including the Inoue Young Scientist Award from the Inoue Foundation for Science in Japan, and Charles A. King Trust Research Fellowship Award from The Medical Foundation in Boston. He was also nominated for the Young Investigator Award at the 2009 World Molecular Imaging Congress in Montreal, Canada.