Reactive Self‐Assembly and Specific Cellular Delivery of NCO‐sP(EO‐stat‐PO)‐Derived Nanogels

AbstractThis study presents the reactive self‐assembly of isocyanate functional and amphiphilic six‐arm, star‐shaped polyether prepolymers in water into nanogels. Intrinsic molecular amphiphilicity, mainly driven by the isophorone moiety at the distal endings of the star‐shaped molecules, allows for the preparation of spherical particles with an adjustable size of 100–200 nm by self‐assembly and subsequent covalent cross‐linking without the need for organic solvents or surfactants. Covalent attachment of a fluorescence dye and either the cell‐penetrating TAT peptide or a random control peptide sequence shows that only TAT‐labeled nanogels are internalized by HeLa cells. The nanogels thus specifically enter the cells and accumulate in the perinuclear area in a time‐ and concentration‐dependent manner.