Multifunctional Trackable Dendritic Scaffolds and Delivery Agents

摘要

We have introduced a novel strategy for the facile synthesis of orthogonally functionalized hybrid dendritic-linear delivery systems, incorporating reactive groups at the chain ends as well as internally, through a combination of "amine-epoxy" and "thiol-yne" click chemistry. Starting from bis-amino-PEG, a fourth-generation dendritic scaffold having chain-end amino groups, a single FITC or Alexa dye, and 20 internal coumarin units could be prepared. Even with this high loading of coumarin units (ca. 25 wt%), confocal microscopy on living cells revealed that upon membrane binding and internalization of the scaffold, intracellular enzymes cleaved the coumarin payload, allowing release into the cytoplasm. As a result, both the dendritic scaffold and the release of its payload can be monitored simultaneously inside living cells.