PURPOSE: To study the effect of sequentially changing the chain length, oxidation level, and charge distribution in N4,N9-diacyl and N4,N9-dialkyl spermines on siRNA formulation, and then to compare their lipoplex transfection efficiency in cell lines. METHODS: Eight N4,N9-diacyl polyamines: N4,N9-[didecanoyl, dilauroyl, dimyristoyl, dimyristoleoyl, dipalmitoyl, distearoyl, dioleoyl and diretinoyl]-1,12-diamino-4,9-diazadodecane were synthesized. Their abilities to bind to siRNA and form nanoparticles were studied using a RiboGreen intercalation assay and particle sizing. Two diamides were also reduced to afford tetraamines N4,N9-distearyl- and N4,N9-dioleyl-1,12-diamino-4,9-diazadodecane. Delivery of fluorescein-labelled Label IT RNAi Delivery Control was studied in FEK4 primary skin cells and in an immortalized cancer cell line (HtTA), and compared with TransIT-TKO. RESULTS: The design, synthesis, and structure-activity relationship studies of a series of N4,N9-disubstituted spermines as efficient vectors for non-viral siRNA delivery to primary skin and cancer cell lines is reported. These non-liposomal cationic lipids are promising siRNA carriers based on the naturally occurring polyamine spermine showing that C-18 is a better chain length as shorter chains are more toxic. CONCLUSIONS: N4,N9-Distearoyl spermine and N4,N9-dioleoyl spermine are efficient siRNA formulation and delivery vectors, even in the presence of serum, comparable to TransIT-TKO. However, four positive charges distributed as in spermine was significantly more toxic.
PURPOSE: To study the effect of sequentially changing the chain length, oxidation level, and charge distribution in N4,N9-diacyl and N4,N9-dialkyl spermines on siRNA formulation, and then to compare their lipoplex transfection efficiency in cell lines. METHODS: Eight N4,N9-diacyl polyamines: N4,N9-[didecanoyl, dilauroyl, dimyristoyl, dimyristoleoyl, dipalmitoyl, distearoyl, dioleoyl and diretinoyl]-1,12-diamino-4,9-diazadodecane were synthesized. Their abilities to bind to siRNA and form nanoparticles were studied using a RiboGreen intercalation assay and particle sizing. Two diamides were also reduced to afford tetraaminesN4,N9-distearyl- and N4,N9-dioleyl-1,12-diamino-4,9-diazadodecane. Delivery of fluorescein-labelled Label IT RNAi Delivery Control was studied in FEK4 primary skin cells and in an immortalized cancer cell line (HtTA), and compared with TransIT-TKO. RESULTS: The design, synthesis, and structure-activity relationship studies of a series of N4,N9-disubstituted spermines as efficient vectors for non-viral siRNA delivery to primary skin and cancer cell lines is reported. These non-liposomal cationic lipids are promising siRNA carriers based on the naturally occurring polyamine spermine showing that C-18 is a better chain length as shorter chains are more toxic. CONCLUSIONS:N4,N9-Distearoyl spermine and N4,N9-dioleoyl spermine are efficient siRNA formulation and delivery vectors, even in the presence of serum, comparable to TransIT-TKO. However, four positive charges distributed as in spermine was significantly more toxic.
Authors: P Kreiss; B Cameron; R Rangara; P Mailhe; O Aguerre-Charriol; M Airiau; D Scherman; J Crouzet; B Pitard Journal: Nucleic Acids Res Date: 1999-10-01 Impact factor: 16.971
Authors: F E Ruiz; J P Clancy; M A Perricone; Z Bebok; J S Hong; S H Cheng; D P Meeker; K R Young; R A Schoumacher; M R Weatherly; L Wing; J E Morris; L Sindel; M Rosenberg; F W van Ginkel; J R McGhee; D Kelly; R K Lyrene; E J Sorscher Journal: Hum Gene Ther Date: 2001-05-01 Impact factor: 5.695
Authors: Elena Matsa; James E Dixon; Christopher Medway; Orestis Georgiou; Minal J Patel; Kevin Morgan; Paul J Kemp; Andrew Staniforth; Ian Mellor; Chris Denning Journal: Eur Heart J Date: 2013-03-06 Impact factor: 29.983