Biodegradable cyclen-based linear and cross-linked polymers as non-viral gene vectors

Abstract Several 1,4,7,10-tetraazacyclododecane (cyclen)-based linear ( 3a – c ) and cross-linked ( 8a – d ) polymers containing biodegradable ester or disulfide bonds were described. These polymeric compounds were prepared by ring-opening polymerization from various diol glycidyl ethers. The molecular weights of the title polymers were measured by GPC. Agarose gel retardation assays showed that these compounds have good DNA-binding ability and can completely retard plasmid DNA (pDNA) at weight ratio of 20 for linear polymers and 1.2 for cross-linked polymers. The degradation of these polymers was confirmed by GPC. The formed polyplexes have appropriate sizes around 400 nm and zeta-potential values about 15–40 mV. The cytotoxicities of 8 assayed by MTT are much lower than that of 25 KDa PEI. In vitro transfection toward A549 and 293 cells showed that the transfection efficiency (TE) of 8c -DNA polyplex is close to that of 25 kDa PEI at 8c /DNA weight ratio of 4. Structure–activity relationships (SAR) of these linear and cross-linked polymers were discussed in their DNA-binding, cytotoxicity, and transfection studies. In addition, in the presence of serum, the TE of 8 /DNA polyplexes could be improved by introducing chloroquine or Ca 2+ to pretreated cells.