A Quantitative Metal-Encoded Conjugate Platform for Targeting Ligand Discovery

The indiscriminate biodistribution of therapeutics can be a key barrier to their safety and efficacy. Localization of compounds into non-diseased tissues often leads to both toxic and dose-limiting effects. To overcome this barrier, nanomedicine implements targeting agents to localize or selectively uptake drugs at disease sites. However, to date there are only a small number of targeting agents with limited scope for targeting tissues. Small-molecule ligands are particularly attractive as targeting agents due to their relatively low cost, tunability, and ease of conjugation. Currently, there are no systematic approaches to the discovery of new small-molecule targeting ligands. Here, we developed a quantitative metal-encoded conjugate platform to determine the biodistribution of multiple small molecules in vivo. By utilizing lanthanide metal complexes, this platform successfully distinguished known ligands with differential tissue targeting in vivo. This system will facilitate the discovery of small molecules as targeting ligands and can accelerate the identification of novel biological targets for tissue-targeted drug delivery.