title: Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection.
abstract: The implementation of RNAi technology into the clinical practice has been significantly postponing due to the issues regarding to the delivery of naked siRNA predominantly to target cells. Here we report the approach to enhance the efficiency of siRNA delivery by encapsulating the siRNA into new carrier systems which are obtained via the combination of widely used layer-by-layer technique and in situ modification by sol-gel chemistry. We used three types of siRNAs (NP-717, NP-1155 and NP-1496) in encapsulated form as new therapeutic agents against H1N1 influenza virus infection. By employing the hybrid microcontainers for the siRNA encapsulation we demonstrate the reduction of viral nucleoprotein (NP) level and inhibition of influenza virus production in infected cell lines (MDCK and A549). The obtained hybrid carriers based on assembled biodegradable polyelectrolytes and sol-gel coating possess several advantages such as a high cell uptake efficiency, low toxicity, efficient intracellular delivery of siRNAs and the protection of siRNAs from premature degradation before reaching the target cells. These findings underpin a great potential of versatile microencapsulation technology for the development of anti-viral RNAi delivery systems against influenza virus infection.
authors.affiliation: RASA center in Tomsk, Tomsk Polytechnic University, Lenin Avenue, 30, 634050, Tomsk, Russian Federation. a_timin@mail.ru.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Timin
authors.affiliation: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, 197022, Saint-Petersburg, Russian Federation.|RASA center in St. Petersburg, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya, 29, 195251, St. Petersburg, Russian Federation.
authors.forename: Albert R
authors.initials: AR
authors.lastname: Muslimov
authors.affiliation: Research Institute of Influenza, Popova str., 15/17, 197376, Saint-Petersburg, Russian Federation.
authors.forename: Aleksandra V
authors.initials: AV
authors.lastname: Petrova
authors.affiliation: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, 197022, Saint-Petersburg, Russian Federation.
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Lepik
authors.affiliation: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, 197022, Saint-Petersburg, Russian Federation.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Okilova
authors.affiliation: Research Institute of Influenza, Popova str., 15/17, 197376, Saint-Petersburg, Russian Federation.|Department of Molecular Biology, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya, 29, 195251, St. Petersburg, Russian Federation.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Vasin
authors.affiliation: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, 197022, Saint-Petersburg, Russian Federation.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Afanasyev
authors.affiliation: School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, E1 4NS, London, UK. g.sukhorukov@qmul.ac.uk.
authors.forename: Gleb B
authors.initials: GB
authors.lastname: Sukhorukov
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002214:Capsules; D004285:Dogs; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D019590:Nucleocapsid Proteins; D000071228:Polyelectrolytes / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D002214:Capsules; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D000071228:Polyelectrolytes; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins