title: SPANosomes as delivery vehicles for small interfering RNA (siRNA).
abstract: Nonionic surfactant vesicles, or SPANosomes (SPs), comprised of cationic lipid and sorbitan monooleate (Span 80) were synthesized and evaluated as small interfering RNA (siRNA) vectors. The SPs had a mean diameter of less than 100 nm and exhibited excellent colloidal stability. The SP/siRNA complexes possessed a slightly positive zeta potential of 12 mV and demonstrated a high siRNA incorporation efficiency of greater than 80%. Cryogenic transmission electron microscopy (cryo-TEM) imaging of the SP/siRNA indicated a predominantly core-shell structure. The SP/siRNA complexes were shown to efficiently and specifically silence expression of both green fluorescent protein (GFP) (66% knockdown) and aromatase (77% knockdown) genes in breast cancer cell lines. In addition, the cellular trafficking pathway of the SP/siRNA was investigated by confocal microscopy using molecular beacons as probes for cytosolic delivery. The results showed efficient endosomal escape and cytosolic delivery of the siRNA cargo following internalization of the SP/siRNA complexes. In conclusion, Span 80 is a potent helper lipid, and the SPs are promising vehicles for siRNA delivery.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhou
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Mao
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Naveen
authors.initials: N
authors.lastname: Kanthamneni
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brueggemeier
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D001141:Aromatase / Q000235:genetics; D045744:Cell Line, Tumor; D020285:Cryoelectron Microscopy; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D006601:Hexoses / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D015345:Oligonucleotide Probes / Q000032:analysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D005229:Fatty Acids, Monounsaturated; D006601:Hexoses; D008081:Liposomes; D015345:Oligonucleotide Probes; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; C018665:sorbitan monooleate; D014810:Vitamin E; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D001141:Aromatase; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; C014225:tocophersolan