Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T-1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T-1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. (C) 2016 Elsevier B.V. All rights reserved.
[1]Tongji Univ, Tongji Hosp, Dept Radiol, Sch Med, Shanghai 200065, Peoples R China.
[2]Tongji Univ, Inst Translat Nanomed, Shanghai East Hosp, Inst Biomed Engn & Nanosci,Sch Med, Shanghai 200092, Peoples R China.
[3]Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200040, Peoples R China.
[4]Tongji Univ, Inst Nano & Biopolymer Mat, Sch Mat Sci & Engn, 4800 Caoan Rd, Shanghai 201804, Peoples R China.
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