Bifunctional and Bioreducible Dendrimer Bearing a Fluoroalkyl Tail for Efficient Protein Delivery Both <i>In Vitro</i> and <i>In Vivo</i>

Rational design of stimuli-responsive polymers for cytosolic protein delivery with robust efficiency is of great importance but remains a challenging task. Here, we reported a bioreducible and amphiphilic dendrimer bearing a fluoroalkyl tail for this purpose. The fluorolipid was conjugated to the focal point of a cysteamine-cored polyamidoamine dendrimer via disulfide bond, while phenylboronic acid moieties were decorated on dendrimer surface for efficient protein binding. The yielding polymer showed high protein binding capability and complex stability and could efficiently release the cargo proteins in a glutathione-responsive manner. The designed polymer was effective in the delivery of various membrane-impermeable proteins into living cells with reserved bioactivities. In addition, the polymer efficiently delivered a toxin protein saporin into 4T1 breast cancer cells and inhibited the tumor growth <i>in vivo</i> after intravenous injection. The developed polymer in this study is a promising vector for the delivery of membrane-impermeable proteins to treat various diseases.