title: Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.
abstract: Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide.
  
  
  BACKGROUND
  This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides.
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sepúlveda-Crespo
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lorente
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.affiliation: Departamento de Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Departamento de Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: De la Mata
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Electronic address: jjimenezf.hgugm@salud.madrid.org.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Jiménez
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Electronic address: mmunoz.hgugm@gmail.com.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D050091:Dendrimers; D012821:Silanes; C504072:carbosilane
keywords: Antiretroviral; Carbosilane dendrimer; HIV prevention; Microbicide; Synergy