Structure-activity relationships of fluorinated dendrimers in DNA and siRNA delivery.
Fluorinated dendrimers have shown great promise in gene delivery due to their high transfection efficacy and low cytotoxicity, however, the structure-activity relationships of these polymers still remain unknown. Herein, we synthesized a library of fluorinated dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results show that fluorination significantly improves the transfection efficacy of G4-G7 polyamidoamine dendrimers in DNA and siRNA delivery. Fluorination on generation 5 dendrimer yields the most efficient polymers in gene delivery, and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. All the fluorinated dendrimers cause minimal toxicity on the transfected cells at their optimal transfection conditions. This study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers.



The structure-activity relationships of fluorinated dendrimers in gene delivery is still unknown and the behavior of fluorinated dendrimers in siRNA delivery has not yet been investigated. Herein, we synthesized a library of fluorinated PAMAM dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results clearly indicate that fluorination significantly improves the transfection efficacy of dendrimers in both DNA and siRNA delivery without causing additional toxicity. G5 PAMAM dendrimer is best scaffold to synthesize fluorinated dendrimers and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. This systematic study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
Mingming
M
Wang
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China. Electronic address: yycheng@mail.ustc.edu.cn.
Yiyun
Y
Cheng
D001583:Benzoxazoles / Q000378:metabolism; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054879:Halogenation; D006367:HeLa Cells; D006801:Humans; D011806:Quinolinium Compounds / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D001583:Benzoxazoles; D050091:Dendrimers; D011806:Quinolinium Compounds; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; C075296:1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium; D049452:Green Fluorescent Proteins; D004247:DNA
Dendrimer; Fluorination; Gene delivery; Structure-activity relationship; siRNA