Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection.
Despite the use of siRNA in the downregulation of HIV-1 replication which has been reported, CD4 T lymphocytes are difficult to transfect with non-viral vectors. We determined whether second generation carbosilane dendrimers (2G-NN16 and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers were also tested on macrophages to determine whether they can modify macrophage phenotype and induce an inflammatory response. The nanoconjugate formed by 2G-03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers presented safety properties because they did not induce proliferation on CD4 T lymphocytes and decrease the release of TNFα and IL-12p40 by macrophages. Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24 dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for gene therapy applications, mainly in the treatment of HIV infection.
Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Ana Judith
AJ
Perisé-Barrios
Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
José Luis
JL
Jiménez
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Angeles
A
Domínguez-Soto
Dpto. de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
F Javier
FJ
de la Mata
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Angel L
AL
Corbí
Dpto. de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Rafael
R
Gomez
Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. Electronic address: mmunoz.hgugm@gmail.com.
María Ángeles
MÁ
Muñoz-Fernandez
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D050091:Dendrimers / Q000008:administration & dosage*; D015693:Gene Products, nef / Q000235:genetics; D018014:Gene Transfer Techniques; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D017646:Organosilicon Compounds / Q000008:administration & dosage*; D010587:Phagocytosis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012821:Silanes / Q000008:administration & dosage*; D014779:Virus Replication / Q000187:drug effects
C000594597:2G-03NN24; C572050:2G-NN16; D016207:Cytokines; D050091:Dendrimers; D015693:Gene Products, nef; D008070:Lipopolysaccharides; D017646:Organosilicon Compounds; D034741:RNA, Small Interfering; D012821:Silanes
CD4 lymphocytes and macrophages; Carbosilane dendrimers; Gene therapy; HIV infection; siRNA delivery