To develop a multifunctional polymeric carrier for gene and drug co-delivery, a new cyclodextrin derivative containing poly(L-lysine) dendrons was prepared by the click conjugation of per-6-azido-beta-cyclodextrin with propargyl focal point poly(L-lysine) dendron of third generation and then characterized by FTIR, H-1 NMR, and GPC analyses. It was found that such a conjugate could form colloidally stable nano-complexes with plasmid DNA in aqueous system and exhibited high gene transfection efficiency. Moreover, it could load efficiently methotrexate drug with anticancer activity and showed a sustained release behavior. Different from commonly used amphiphilic copolymers with cationic character, the as obtained cyclodextrin derivative may be used directly for the combinatorial delivery of nucleic acid and lipophilic anticancer drugs without a complicated micellization process. (C) 2013 Elsevier Inc. All rights reserved.