Urocanic acid improves transfection efficiency of polyphosphazene with primary amino groups for gene delivery.
The biodegradable cationic poly(2-(2-aminoethoxy)ethoxy)phosphazene (PAEP) bearing primary amino groups and a new PAEP derivative, urocanic acid (UA) modified PAEP (UA-PAEP), were synthesized and investigated for gene delivery. The results indicated that PAEP was able to condense DNA into complex nanoparticles with the size around 120 nm at the polymer/DNA ratio (N/P) of 35, at which PAEP/DNA complex nanoparticles (PACNs) showed efficient transfection activity in complete medium. After conjugating with UA at the substitution degree of 7% (UA-PAEP7), UA-PAEP7/DNA complex nanoparticles (UP7CNs) exhibited higher transfection efficiency than PACNs and UA-PAEP25/DNA complex nanoparticles (UP25CNs) and much lower cytotoxicity compared with PEI/DNA complex nanoparticles (PEICNs). The transfection experiment using a proton pump inhibitor suggested that the gene expression of PACNs and UP-PAEP/DNA complex nanoparticles (UPCNs) was dependent on the endosomal acidification process. The acetate solution (20 mM, pH5.7) improved the transfection activity of UP7CNs in HeLa and COS 7 cell lines, which was almost comparable to PEICNs at the N/P ratio of 35. Therefore, the results suggested that UP7CNs could be a promising carrier for gene delivery.
Yang
Yongxin
Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Zhiwen
Z
Chen
Lingli
L
Gu
Wangwen
W
Li
Yaping
Y
D000588:Amines / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006579:Heterozygote; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D010957:Plasmids; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014162:Transfection / Q000379:methods*; D014560:Urocanic Acid / Q000737:chemistry* / Q000493:pharmacokinetics
D000588:Amines; D005021:Ethylamines; D009943:Organophosphorus Compounds; D011108:Polymers; C000597215:poly(2-(2-aminoethoxy)ethoxy)phosphazene; D004247:DNA; D014560:Urocanic Acid