Linear cationic click polymer for gene delivery: synthesis, biocompatibility, and in vitro transfection.
Sixteen novel cationic click polymers (CPs) were parallelly synthesized via the conjugation of four alkyne-functionalized monomers to four azide-functionalized monomers by "click chemistry". The biocompatibility of CPs was evaluated by in vitro cytotoxicity (MTT assay, Hoechst/PI apoptosis/necrosis assay, and cell cycle analysis) and blood compatibility tests (hemolysis and erythrocyte aggregation). The experimental results showed that the kind of amine groups, charge density, and number of methylene or ethylene glycol groups brought about the effect on toxicity of CPs. Among all polymers, two polymers (B1 and B2) showed good biocompatibility, inducing neither apoptosis nor necrosis at the test concentration and low hemolysis ratio and erythrocyte aggregation. In particular, B1 and B2 exhibited the comparable transfection efficiency compared with PEI (25 kDa) but much lower cytotoxicity. These results suggested that the novel cationic CPs could be promising carriers for gene delivery.
Gao
Yu
Y
Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Chen
Lingli
L
Zhang
Zhiwen
Z
Gu
Wangwen
W
Li
Yaping
Y
D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D002412:Cations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004903:Erythrocyte Aggregation / Q000187:drug effects; D018014:Gene Transfer Techniques; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured
D001672:Biocompatible Materials; D002412:Cations; D011108:Polymers