title: Clustering Small Dendrimers into Nanoaggregates for Efficient DNA and siRNA Delivery with Minimal Toxicity.
abstract: Cationic dendrimers are widely used as nonviral gene vectors, however, current gene materials based on dendrimers are either little effective or too toxic on the transfected cells. Here, a facile strategy is presented to prepare high efficient dendrimers with low transfection toxicity. Small dendrimers with 2 nm are clustered into nanoaggregates (≈100 nm) via phenylboronic acid modification and the self-assembled materials enable efficient DNA and siRNA delivery on several cell lines. The clustered nanostructures can disassemble into small dendrimers in acidic conditions thus exerting significantly less toxicity on the transfected cells. Further structure-function relationship studies reveal that both the phenyl group and boronic acid group play essential roles in the self-assembly and gene delivery processes. The transfection efficacy of phenylboronic acid-modified dendrimers can be down-regulated by blocking the boronic acid groups on dendrimers with diols or degrading the groups with hydrogen peroxide. This study provides a facile strategy in the development of efficient and biocompatible gene vectors based on low molecular weight polymers and clearly demonstrates the structure-function relationship of phenylboronic acid-modified polymers in gene delivery.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China.
authors.forename: Chongyi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China.
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry*; D020868:Gene Silencing / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
chemical_list: D001896:Boron Compounds; D001897:Boronic Acids; D050091:Dendrimers; D011108:Polymers; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C030433:n-butylboronic acid; D004247:DNA; D008156:Luciferases; C010686:benzeneboronic acid
keywords: dendrimers; gene delivery; phenylboronic acid; self-assembly; siRNA