title: Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction.
abstract: This paper examines a perspective on the use of newly engineered nanomaterials as effective and safe carriers of genes for the therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus and carbosilane) were complexed with anticancer siRNA and their biophysical properties of the dendriplexes analyzed. The potential of the dendrimers as nanocarriers for anticancer siBcl-xl, siBcl-2, siMcl-1 siRNAs and a siScrambled sequence was explored. Dendrimer/siRNA complexes were characterized by methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. Some of the experiments were done with heparin to check if siRNA can be easily disassociated from the complexes, and whether released siRNA maintains its structure after interaction with the dendrimer. The results indicate that siRNAs form complexes with all the dendrimers tested. Oligoribonucleotide duplexes can be released from dendriplexes after heparin treatment and the structure of siRNA is maintained in the case of PAMAM or carbosilane dendrimers. The dendrimers were also effective in protecting siRNA from RNase A activity. The selection of the best siRNA carrier will be made based on cell culture studies (Part B).
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of 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, Poland.
authors: Joanna
authors: J
authors: Lazniewska
authors: Institute of Biophysics and Cell Engineering of NASB, Minsk, Belarus.
authors: Volha
authors: V
authors: Dzmitruk
authors: Institute of Biophysics and Cell Engineering of NASB, Minsk, Belarus.
authors: Inessa
authors: I
authors: Halets
authors: Institute of Biophysics and Cell Engineering of NASB, Minsk, Belarus.
authors: Svetlana
authors: S
authors: Loznikova
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: Evgeny
authors: E
authors: Apartsin
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
authors: Olga
authors: O
authors: Krasheninina
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
authors: Alya
authors: A
authors: Venyaminova
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors: Katarzyna
authors: K
authors: Milowska
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors: Olga
authors: O
authors: Nowacka
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: Gomez-Ramirez
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: Francisco Javier
authors: FJ
authors: de la Mata
authors: Laboratorie de Chimie de Coordination, CNRS, Toulouse, France.
authors: Jean-Pierre
authors: JP
authors: Majoral
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, Poland.
authors: Maria
authors: M
authors: Bryszewska
mesh_terms: D002942:Circular Dichroism; D050091:Dendrimers / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D015972:Gene Expression Regulation, Neoplastic; 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*; 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*; 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; Biophysical characteristics; Complex formation; Dendrimer; Nano-drug-delivery