title: Shell-cross-linked micelles containing cationic polymers synthesized via the RAFT process: toward a more biocompatible gene delivery system.
abstract: Block copolymers poly(2-(dimethylamino) ethyl methacrylate)-b-poly(polyethylene glycol methacrylate) (PDMAEMA-b-P(PEGMA)) were prepared via reversible addition fragmentation chain transfer polymerization (RAFT). The polymerization was found to proceed with the expected living behavior resulting in block copolymers with varying block sizes of low polydispersity (PDI <1.3). The resulting block copolymer was self-assembled in an aqueous environment, leading to the formation of pH-responsive micelles. Further stabilization of the micellar system was performed in water using ethylene glycol dimethacrylate and the RAFT process to cross-link the shell. The cross-linked micelle was found to have properties significantly different from those of the uncross-linked block copolymer micelle. While a distinct critical micelle concentration (CMC) was observed using block copolymers, the CMC was absent in the cross-linked system. In addition, a better stability against disintegration was observed when altering the ionic strength such as the absence of changes of the hydrodynamic diameter with increasing NaCl concentration. Both cross-linked and uncross-linked micelles displayed good binding ability for genes. However, the cross-linked system exhibited a slightly superior tendency to bind oligonucleotides. Cytotoxicity tests confirmed a significant improvement of the biocompatibility of the synthesized cross-linked micelle compared to that of the highly toxic PDMAEMA. The cross-linked micelles were taken up by cells without causing any signs of cell damage, while the PDMAEMA homopolymer clearly led to cell death.
authors: Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
authors: Ling
authors: L
authors: Zhang
authors: T L Uyen
authors: TL
authors: Nguyen
authors: Julien
authors: J
authors: Bernard
authors: Thomas P
authors: TP
authors: Davis
authors: Christopher
authors: C
authors: Barner-Kowollik
authors: Martina H
authors: MH
authors: Stenzel
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis*; D001672:Biocompatible Materials / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D008689:Methacrylates; D008823:Micelles; C524500:poly(2-(dimethylamino) ethyl methacrylate)-b-poly(polyethylene glycol methacrylate); C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; C049840:2-(dimethylamino)ethyl methacrylate