The pH-responsive hyperbranched star copolymers HP(DMAESP-co-BS2MOE)(POEGMA)ns have been successfully synthesized via two-step atom transfer radical polymerization (ATRP).The first step is polymerization of methacryloyloxy-3-thiahexanoyl-N

N-dimethyl acetate (DMAESP) and 2-(2'-bromoisobutyryloxy) ethyl 2-methacryloyl oxyethyl disulfide (BS2MOE).GPC analysis of HP(DMAESP-co-BS2MOE) had a relatively wide molecular weight distribution and showed a double peak

which is consistent with the feature of hyperbranched polymers prepared by self-condensing vinyl polymerization.The resultant HP(DMAESP-co-BS2MOE) was used as macroinitiator in the subsequent ATRP of oligo(ethylene glycol) methacrylate (OEGMA).The molecular weights of the resultant hyperbranched star polymers apparently increased in comparison with HP(DMAESP-co-BS2MOE)

but the polydispersity indexes decreased with the increase of polymerization time.In DMAESP

the methacrylate unit and tertiary amine group is linked by an acid-labile -thiopropionate linker

which can be slowly degraded under mild acidic conditions (pH=5.0) to form carboxylic acid terminals

thus the HP(DMAESP-co-BS2MOE)(POEGMA)ns exhibit pH-responsive charge conversion behavior

which is highly favored in gene delivery application.Hyperbranched star copolymers containing disulfide bonds can be further degraded in the presence of glutathione in cytosol.When the hyperbranched star copolymers are self-assembled in water

micelles with the HP(DMAESP-co-BS2MOE) core and the POEGMA shell are formed.Transmission electron microscopy images showed formation of the spherical micelles.The average diameters of the micelles measured by DLS are in the range of 138 to 226 nm

after treated with 10 mmol/L DTT for 24 h

their diameters changed to 21 to 32 nm

and their molecular weights also significantly decreased.The experiments in vitro were performed on HepG2 cells

the micelles formed by HP(DMAESP-co-BS2MOE)(POEGMA)n showed relatively low cytotoxicity comparing to PEI 25K and high DNA loading efficiency.After the internalization of as prepared polyplex

and the charge of the micelles was conversed to negative poly-ion

the efficient release of the loaded DNA was observed

and the micelles can be cleaved by GSH at the same time to further reduce the cyto-toxicity.Therefore

this system shows promising future as gene delivery application.