Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas

Targeted drug delivery to pancreatic islet β cells is an unmet clinical need. β cells possess a uniquely high Zn²⁺ concentration, and integrating Zn²⁺-binding activity into a small molecule can bias drug accumulation and activity toward β cells. This protocol can be used to evaluate a molecule's capacity to chelate islet Zn²⁺, accumulate in islets, and stimulate β cell-selective replication in mouse pancreas. One obstacle is establishing an LC-MS/MS-based method for compound measurement. Limitations include target compound ionizability and the time-sensitive nature of some experimental assay steps. For complete details on the use and execution of this protocol, please refer to Horton et al. (2019).