title: Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action.
abstract: This paper examines a perspective to use newly engineered nanomaterials as effective and safe carriers for gene therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus, and carbosilane) were complexed with anticancer siRNA and the biophysical properties of the dendriplexes created were analyzed. The potential of the dendrimers as nanocarriers for anticancer Bcl-xl, Bcl-2, Mcl-1 siRNAs and additionally a scrambled sequence siRNA has been explored. Dendrimer/siRNA complexes were characterised by various methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. In this part of study, the transfection of complexes in HeLa and HL-60 cells was analyzed using both single apoptotic siRNAs and a mixture (cocktail) of them. Cocktails were more effective than single siRNAs, allowing one to decrease siRNAs concentration in treating cells. The dendrimers were compared as siRNA carriers, the most effective being the phosphorus-based ones. However, they were also the most cytotoxic on their own, so that in this regard the application of all dendrimers in anticancer therapy will be discussed.
authors: Institute of Biophysics and Cell Engineering of NASB, Minsk, Belarus.
authors: Volha
authors: V
authors: Dzmitruk
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: Aleksandra
authors: A
authors: Szulc
authors: Institute of Biophysics and Cell Engineering of NASB, Minsk, Belarus. Electronic address: shcharbin@gmail.com.
authors: Dzmitry
authors: D
authors: Shcharbin
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: Anna
authors: A
authors: Janaszewska
authors: Republican Research and Practical Center of Neurology and Neurosurgery, Minsk, Belarus.
authors: Natallia
authors: N
authors: Shcharbina
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: Joanna
authors: J
authors: Lazniewska
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
authors: Darya
authors: D
authors: Novopashina
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
authors: Marina
authors: M
authors: Buyanova
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. Electronic address: maksion@biol.uni.lodz.pl.
authors: Maksim
authors: M
authors: Ionov
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; Leibniz-Institut fur Polymerforschung Dresden e.V., HoheStrasse 6,01069 Dresden, Germany.
authors: Barbara
authors: B
authors: Klajnert-Maculewicz
authors: Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain.
authors: Rafael
authors: R
authors: Gómez-Ramirez
authors: Université Paris Descartes, PRES Sorbonne Paris Cité, CNRS UMR, 860, Paris, France.
authors: Serge
authors: S
authors: Mignani
authors: Laboratorie de Chimie de Coordination, CNRS, Toulouse, France.
authors: Jean-Pierre
authors: JP
authors: Majoral
authors: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain; Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Maria Angeles
authors: MA
authors: Muñoz-Fernández
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: Maria
authors: M
authors: Bryszewska
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D002942:Circular Dichroism; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D004587:Electrophoresis, Agar Gel; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008027:Light; D046529:Microscopy, Electron, Transmission; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009690:Nucleic Acid Conformation; D010316:Particle Size; D010758:Phosphorus / Q000737:chemistry* / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D012542:Scattering, Radiation; D012821:Silanes / Q000737:chemistry* / Q000633:toxicity; D013050:Spectrometry, Fluorescence; D014162:Transfection / Q000379:methods*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D050091:Dendrimers; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C104700:PAMAM Starburst; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D012821:Silanes; D051020:bcl-X Protein; C504072:carbosilane; D010758:Phosphorus; D006493:Heparin
keywords: Anticancer siRNA; Cancer cells; Dendrimer; Nano-drug-delivery