Enzyme triggered disassembly of amphiphilic linear-dendritic block copolymer micelles based on poly[N-(2-hydroxyethyl-l-glutamine)]

Well-defined enzyme-responsive amphiphilic linear-dendritic diblock copolymers G-b-PHEG and bis-MPA-G(n)-b-PHEG (n = 1, 2) based on a hydrophilic linear block of poly(hydroxyethyl l-glutamine) (PHEG) and a hydrophobic dendron derived from cysteamine or an aliphatic polyester of 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) have been synthesized for the first time via a combination of the dendron-first strategy and the ring-opening polymerization of -amino acid N-carboxyanhydrides (NCA). The obtained copolymers G-b-PHEG and bis-MPA-G(n)-b-PHEG (n = 1, 2) were characterized by gel permeation chromatography (GPC), Fourier transfrom-infrared spectroscopy (FT-IR), and H-1 NMR spectroscopy. These amphiphilic copolymers are able to form nanospherical micelles or vesicles in aqueous solution as revealed by H-1 NMR analyses of the micelles in D2O, fluorescence spectroscopy, transmission electron microscopy (TEM) and particle size analysis. The self-assembled micelles show good enzyme-responsiveness, which can disassemble and release the encapsulated hydrophobic Nile red upon enzymatic activation. In vitro cytotoxicity studies indicate that the copolymers have good compatibility with SMMC-7721 cells. Such smart amphiphilic copolymers could potentially be applied for drug delivery systems and biosensors.