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Title: Polyanionic carbosilane dendrimers as a new adjuvant in combination with latency reversal agents for HIV treatment
Authors: Relaño-Rodríguez, Ignacio
Juárez-Sánchez, Raquel
Pavicic, Carolina
Muñoz, Eduardo
Muñoz-Fernández, Maria Ángeles
metadata.dc.contributor.authoraffiliation: [Relaño-Rodríguez,I; Juárez-Sánchez,R; Muñoz-Fernández,MA] Molecular Immunology Laboratory, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Relaño-Rodríguez,I; Juárez-Sánchez,R; Muñoz-Fernández,MA] Health Research Institute Gregorio Marañón (IiSGM), Spanish HIV HGM BioBank, Madrid, Spain.[Relaño-Rodríguez,I; Juárez-Sánchez,R; Muñoz-Fernández,MA] Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. [Relaño-Rodríguez,I; Pavicic,C] Innohealth, Parque Científico de Madrid, Madrid, Spain. [Muñoz,E] Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigaciones Biomédicas de Córdoba (IMIBIC)/Reina Sofia University Hospital University of Córdoba, Córdoba, Spain.
Keywords: Nanomedicine;Dendrimers;HIV-1 latency;Latency reversal agents;Nanomedicina;Dendrímeros;VIH-1;Latencia del virus
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Adjuvants, Immunologic
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Bryostatins
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Survival
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Dendrimers
Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Depsipeptides
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination
Medical Subject Headings::Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections
Medical Subject Headings::Organisms::Viruses::Vertebrate Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes
Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Mononuclear Phagocyte System::Monocytes
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Particle Size
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Organosilicon Compounds::Silanes
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Surface Properties
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents
Issue Date: 21-May-2019
Citation: Relaño-Rodríguez I, Juárez-Sánchez R, Pavicic C, Muñoz E, Muñoz-Fernández MA. Polyanionic carbosilane dendrimers as a new adjuvant in combination with latency reversal agents for HIV treatment. 2019;17(1):69.
Abstract: Background: The major obstacle impeding human immunodeficiency virus-1 (HIV-1) eradication in antiretroviral treatment (ART) treated HIV-1 subjects is the establishment of long-lived latently infected resting CD4+ T cells. Due to the fact that no drug has been effective, the search for new drugs and combinations are a priority in the HIV cure. Treatments based on nanotechnology have emerged as an innovative and promising alternative to current and conventional therapies. In this respect, nanotechnology opens up a new door for eliminating latent HIV infection. We studied the role of G1-S4, G2-S16 and G3-S16 polyanionic carbosilane dendrimers in the context of latent HIV-1 persistence. Moreover, we study the efficiency of these dendrimers in combination with latency reversal agents (LRAs) against HIV-1 infection. Methods: J89GFP lymphocyte and THP89GFP monocyte derived cell lines latently infected with HIV-1 p89GFP were used as an in vitro model of latency for our study. Viability assays by 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were performed to determine the working concentrations of dendrimers and LRAs. Both cell lines were treated with G1-S4, G2-S16 and G3-S16 either alone or in combination with bryostatin (BRY), romidepsin (RMD) or panobinostat (PNB) for 24 and 48 h. The expression pattern of GFP was measured by flow cytometry and referred as measure of viral reactivation. Results and discussion: The combination treatment of the dendrimers with the protein kinase C (PKC) agonist did not modify the antilatency activity in J89GFP lymphocyte cell line. Interestingly enough, G3-S16 dendrimer alone and its combination with BRY, RMD or PNB showed a significant increased expression of GFP in the THP89GFP monocyte cell line. Conclusion: We showed for the first time that nanoparticles, in this case, G3-S16 anionic carbosilan dendrimer may play an important role in new treatments against HIV-1 infection.
metadata.dc.identifier.doi: 10.1186/s12951-019-0500-4
ISSN: 1477-3155 (Online)
Appears in Collections:01- Artículos - IMIBIC. Instituto Maimónides de Investigación Biomédica de Córdoba

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