Evaluation of various polyethylenimine formulations for light-controlled gene silencing using small interfering RNA molecules.
Photochemical internalization (PCI) is a technology based on a photosensitizer that photochemically destabilizes endosomal membranes after illumination, resulting in the release of endocytosed material into the cytosol. In this study, we investigated the potential of using polyethylenimine (PEI) for light-controlled delivery of small interfering RNA (siRNA) molecules via the endocytic pathway. PEI formulations with different molecular weights (MW) and chemical forms (linear [L]/branched [B]) were investigated for their capacity to deliver siRNA molecules with or without PCI at variable nitrogen/phosphorus (N/P) ratios and illumination doses. By targeting the S100A4 gene in an osteosarcoma cell model system, potent gene silencing was observed in samples treated with PCI compared with samples not treated with PCI. The effect of light-controlled gene silencing was dependent on several factors, including light-doses and MW, chemical form, as well as on the N/P ratio of the PEI formulations. This study demonstrates the first success in using PEI formulations as siRNA carriers for light-controlled gene silencing with the objective of future use in in vivo applications.
Boe
Sigurd
S
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. sigurdbo@rr-research.no
Longva
Ane S
AS
Hovig
Eivind
E
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D020868:Gene Silencing / Q000528:radiation effects*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008027:Light; D008970:Molecular Weight; D009584:Nitrogen / Q000737:chemistry; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D010758:Phosphorus / Q000737:chemistry; D017319:Photosensitizing Agents; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics; D014162:Transfection
D017319:Photosensitizing Agents; D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D010758:Phosphorus; D011094:Polyethyleneimine; D009584:Nitrogen