title: 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.
authors.affiliation: Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and West China Hospital, Sichuan University, Chengdu 610064, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Shi-Fei
authors.initials: SF
authors.lastname: Wu
authors.forename: Bo-Lin
authors.initials: BL
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D020341:Absorbable Implants; D003432:Cross-Linking Reagents / Q000737:chemistry*; D000080027:Cyclams; D005822:Genetic Vectors / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D003432:Cross-Linking Reagents; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011108:Polymers; C038072:cyclen