Synthesis of 6-N,N,N-trimethyltriazole chitosan via "click chemistry" and evaluation for gene delivery.
The selective introduction of a trimethylammonium cationic group into the C-6 position of chitosan (Cs) was successfully performed by "click chemistry" for the first time, and the 6-N,N,N-trimethyltriazole-Cs (TCs) showed good solubility in water. TCs showed strong DNA binding ability and high protection of DNA against nuclease degradation assessed by gel electrophoresis assay. TCNs showed lower degree of flocculation than Cs/DNA self-assembled nanoparticles (CsNs) in the presence of medium containing serum within 60 min. The introduction of trimethyltriazole group led to significantly increased cellular uptake compared with unmodified Cs, which resulted in higher transfection efficiency in HEK 293 and MDA-MB-468 cells. TCs were noncytotoxic, and viability of cells exposure to TCNs for 24 h was over 80% even at 50 microg/mL of polymer. These results suggested that TCs could be an efficient and safe material for gene delivery.
Gao
Yu
Y
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Zhiwen
Z
Chen
Lingli
L
Gu
Wangwen
W
Li
Yaping
Y
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D048271:Chitosan / Q000138:chemical synthesis* / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D010957:Plasmids / Q000008:administration & dosage; D014162:Transfection; D014230:Triazoles / Q000737:chemistry*
D014230:Triazoles; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D048271:Chitosan