Asymmetrically functionalized β-cyclodextrin-based star copolymers for integrated gene delivery and magnetic resonance imaging contrast enhancement

摘要: We report on the synthesis of star copolymers possessing dual functions gene delivery vectors and magnetic resonance (MR) imaging contrast enhancement. Starting from asymmetrically functionalized β-cyclodextrin (β-CD) comprising 7 azide moieties 14 α-bromopropionate functionalities at upper lower rim a rigid toroidal β-CD core, (DOTA-Gd)7-CD-(PDMA)14 were synthesized via atom transfer radical polymerization (ATRP) N,N-dimethylaminoethyl methacrylate (DMA) subsequent click reaction with an alkynyl-functionalized gadolinium (Gd3+) complex, DOTA-Gd, where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. The obtained Janus-type copolymers, (DOTA-Gd)7-CD-(PDMA)14, could completely complex anionic plasmid DNA (pDNA) electrostatic interactions N/P ratios equal to or higher than 2 exhibit optimal in vitro transfection efficiency ratio 8. In addition, MR experiments demonstrated considerably enhanced T1 relaxivity (r1 ∼ 10.9 s−1 mM−1) for copolymer compared that commercially available small molecular agents (2.4–3.2 mM−1). star-type topology based combination integrated design diagnostic therapeutic augurs well their potential applications field image-guided therapy.