title: Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori.
abstract: Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria.
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto, Portugal.|Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.|i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: Rita S
authors.initials: RS
authors.lastname: Santos
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: George R
authors.initials: GR
authors.lastname: Dakwar
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.|Center for Nano- and Biophotonics, Ghent University, Ghent, Belgium.
authors.forename: Ranhua
authors.initials: R
authors.lastname: Xiong
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.|Center for Nano- and Biophotonics, Ghent University, Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Forier
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Remaut
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stremersch
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto, Portugal.|i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors.forename: Nuno
authors.initials: N
authors.lastname: Guimarães
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto, Portugal.|i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.|Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Fontenete
authors.affiliation: Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Leite
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.affiliation: Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.|Center for Nano- and Biophotonics, Ghent University, Ghent, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Braeckmans
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto, Portugal.
authors.forename: Nuno F
authors.initials: NF
authors.lastname: Azevedo