Protein Delivery to the Cytosol and Cell Nucleus via Micellar Nanocarrier-Based Nonendocytic Uptake

Although efficient cell nucleus delivery of exogenous materials can greatly improve their biochemical activity, this is strictly restricted by cellular uptake and intracellular trafficking processes. In the current approach, synthetic carriers are designed for cell delivery of exogenous materials via endocytosis, and nucleus delivery can be achieved via endosomal escape. Here, we demonstrate that a nonendocytic cell uptake approach can be adapted for protein delivery to the cell nucleus. We have designed a phenylboronic acid-terminated micellar carrier that can bind with protein in the presence of green tea polyphenol and deliver protein into the cytosol via the nonendocytic approach. Using this approach, four different proteins are delivered to the cytosol within 15 min, and low-molecular weight proteins are delivered to the nucleus. The designed approach can be extended for delivering macromolecular drugs to subcellular targets for a more efficient therapy.