Advances in amphiphilic copolymers can potentially be exploited in drug or gene delivery. This study develops novel comb-like amphiphilic copolymers that comprise poly(gamma-glutamic acid) (gamma-PGA) as a hyrdrophilic backbone and Doxifluridine-poly-(epsilon-caprolactone) (5'-deoxy-5-fluorouridine-poly(epsilon-caprolactone), 5'DFUR-PCL) as a hydrophobic side chain. A novel 5'DFUR-PCL polymer was synthesized with antitumor agent Doxifluridine (5'DFUR) as the initiator via the ring-opening polymerization of F-caprolactone (epsilon-CL) using tin(II) 2-ethylhexanoate (Sn(Oct)(2)) as the catalyst. The 5'DFUR-PCL polymer was then grafted on gamma-PGA to yield a 5'DFUR-PCL-gamma-PGA comb-like copolymer with the help of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC). The characteristics of these copolymers were examined by H-1 NMR, FT-IR, GPC, contact angle measurement and thermal properties. Grafting 5'DFUR-PCL would significantly increase the contact angle and decrease the melting temperature (T-m) of the copolymers. The micelles self-assembled from these amphiphilic copolymers were formed in an aqueous phase and were examined via fluorescence approaches, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The average sizes of the micelles were in the range from 130 to 230 nm and their zeta potentials were negative and less than -16.7 mV. The critical micelle concentration (CMC) was from 1.49 mg/L to 4.63 mg/L at 25 degrees C. TEM images demonstrated that the micelles were spherical and clearly had a core-shell structure. (C) 2009 Elsevier Ltd. All rights reserved.