Native Zinc Catalyzes Selective and Traceless Release of Small Molecules in β-Cells
Miseon Lee, Basudeb Maji, Debasish Manna, Sevim Kahraman, Ruth M. Elgamal, Jonnell C. Small, Praveen Kokkonda, Amedeo Vetere, Jacob M. Goldberg, Stephen J. Lippard, Rohit Kulkarni, Bridget K. Wagner, Amit Choudhary
Abstract
or other cell-types in an organismal context will be immensely valuable in advancing diabetes research and therapeutic development. Here, we leverage the unusually high Zn(II) concentration in β-cells to develop a Zn(II)-based prodrug system to selectively and tracelessly deliver bioactive small molecules and fluorophores to β-cells. The Zn(II)-targeting mechanism enriches the inactive cargo in β-cells as compared to other pancreatic cells; importantly, Zn(II)-mediated hydrolysis triggers cargo activation. This prodrug system, with modular components that allow for fine-tuning selectivity, should enable the safer and more effective targeting of β-cells.