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Arginine-Terminated Generation 4 PAMAM Dendrimer as an Effective Nanovector for Functional siRNA Delivery in Vitro and in Vivo

Liu, Cheng ; Liu, Xiaoxuan ; Rocchi, Palma ; Qu, Fanqi ; Iovanna, Juan L ; Peng, Ling

Bioconjugate chemistry, 2014-03, Vol.25 (3), p.521-532 [Periódico revisado por pares]

United States: American Chemical Society

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Título:
Arginine-Terminated Generation 4 PAMAM Dendrimer as an Effective Nanovector for Functional siRNA Delivery in Vitro and in Vivo
Autor: Liu, Cheng ; Liu, Xiaoxuan ; Rocchi, Palma ; Qu, Fanqi ; Iovanna, Juan L ; Peng, Ling
Assuntos: Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Arginine - chemistry ; Biochemistry ; Cell Proliferation - drug effects ; Chemical compounds ; Dendrimers - chemical synthesis ; Dendrimers - chemistry ; Dendrimers - pharmacology ; Dose-Response Relationship, Drug ; Drug Carriers - chemical synthesis ; Drug Carriers - chemistry ; Drug Carriers - pharmacology ; Drug Delivery Systems ; Drug Screening Assays, Antitumor ; Gene Silencing - drug effects ; Humans ; Molecular Structure ; Nanostructures - chemistry ; Polyamines - chemical synthesis ; Polyamines - chemistry ; Polyamines - pharmacology ; Ribonucleic acid ; RNA ; RNA, Small Interfering - chemistry ; RNA, Small Interfering - pharmacology ; Structure-Activity Relationship ; Toxicity ; Tumor Cells, Cultured
É parte de: Bioconjugate chemistry, 2014-03, Vol.25 (3), p.521-532
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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Descrição: Successful therapeutic implementation of RNA interference critically depends on systems able to safely and efficiently deliver small interfering RNA (siRNA). Dendrimers are emerging as appealing nanovectors for siRNA delivery by virtue of their unique well-defined dendritic nanostructure within which is confined an intriguing cooperativity and multivalency. We have previously demonstrated that structurally flexible triethanolamine (TEA) core poly(amidoamine) (PAMAM) dendrimers of high generations are effective nanovectors for siRNA delivery in vitro and in vivo. In the present study, we have developed arginine-terminated dendrimers with the aim of combining and harnessing the unique siRNA delivery properties of the TEA-core PAMAM dendrimer and the cell-penetrating advantages of the arginine-rich motif. A generation 4 dendrimer of this family (G 4 Arg) formed stable dendriplexes with siRNA, leading to improved cell uptake of siRNA by comparison with its nonarginine bearing dendrimer counterpart. Moreover, G 4 Arg was demonstrated to be an excellent nanocarrier for siRNA delivery, yielding potent gene silencing and anticancer effects in prostate cancer models both in vitro and in vivo with no discernible toxicity. Consequently, importing an arginine residue on the surface of a dendrimer is an appealing option to improve delivery efficiency, and at the same time, the dendrimer G 4 Arg constitutes a highly promising nanovector for efficacious siRNA delivery and holds great potential for further therapeutic applications.
Editor: United States: American Chemical Society
Idioma: Inglês

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Arginine-Terminated Generation 4 PAMAM Dendrimer as an Effective Nanovector for Functional siRNA Delivery in Vitro and in Vivo

Liu, Cheng ; Liu, Xiaoxuan ; Rocchi, Palma ; Qu, Fanqi ; Iovanna, Juan L ; Peng, Ling

United States: American Chemical Society

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