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-Gn-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 α-amino acid N-carboxyanhydrides (NCA). The obtained copolymers G-b-PHEG and bis-MPA-Gn-b-PHEG (n = 1, 2) were characterized by gel permeation chromatography (GPC), Fourier transfrom-infrared spectroscopy (FT-IR), and 1H NMR spectroscopy. These amphiphilic copolymers are able to form nanospherical micelles or vesicles in aqueous solution as revealed by 1H 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.