Structure-Inherent Targeting for Bioimaging and Nanomedicine

Two fundamental and unsolved problems facing bioimaging and nanomedicine are nonspecific uptake of intravenously administered therapeutic agents by normal tissues and organs, and incomplete elimination of unbound targeted... [ view full abstract ]

Two fundamental and unsolved problems facing bioimaging and nanomedicine are nonspecific uptake of intravenously administered therapeutic agents by normal tissues and organs, and incomplete elimination of unbound targeted agents from the body. To solve these problems, we have developed a new concept of “structure-inherent targeting” using near-infrared (NIR) fluorophores that combines imaging and tissue-specific targeting components into a single molecule. The compact design enables the contrast agent to be easily cleared by the body, which reduces background signal and makes visualizing signal emitted from the targeted tissue easier.  

On the basis of this “structure-inherent targeting" concept, we have generated a series of targeted contrast agents with systematically varying net charge, conformational shape, hydrophilicity/lipophilicity, and charge distribution that dictate biodistribution and targeting such as thyroid and parathyroid glands (Nat Med. 2015), bone (Angew Chem. 2014), and cartilage (Angew Chem. 2015). Within the new type of contrast agents, the targeting component is incorporated directly into the chemical structure of the fluorophore to reduce the overall size and encourage clearance; thus our study solves two fundamental problems associated with fluorescence image-guided surgery and lays the foundation for additional targeted contrast agents development with optimal optical and in vivo performance.