Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.26/15083 |
Resumo: | This is the author’s version of a work that was accepted for publication in Nanoscale. |
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Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicidesHIV-2 preventionIn vivo miceMicrobicidesMode of actionPolyanionic carbosilane dendrimersThis is the author’s version of a work that was accepted for publication in Nanoscale."The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33–0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans."Royal Society of ChemistryRepositório ComumBriz, VerónicaSepúlveda-Crespo, DanielDiniz, Ana RitaBorrego, PedroRodes, BertaJavier de la Mata, FranciscoGómez, RafaelTaveira, NunoMuñoz-Fernández, Mª Ángeles2016-10-12T08:53:14Z2015-07-01T00:00:00Z2015-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.26/15083engNanoscale. 2015 Sep 21;7(35):14669-83. doi: 10.1039/c5nr03644e2040-337210.1039/C5NR03644Einfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-10-06T14:52:31Zoai:comum.rcaap.pt:10400.26/15083Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:08:22.946519Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| title |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| spellingShingle |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides Briz, Verónica HIV-2 prevention In vivo mice Microbicides Mode of action Polyanionic carbosilane dendrimers |
| title_short |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| title_full |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| title_fullStr |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| title_full_unstemmed |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| title_sort |
Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides |
| author |
Briz, Verónica |
| author_facet |
Briz, Verónica Sepúlveda-Crespo, Daniel Diniz, Ana Rita Borrego, Pedro Rodes, Berta Javier de la Mata, Francisco Gómez, Rafael Taveira, Nuno Muñoz-Fernández, Mª Ángeles |
| author_role |
author |
| author2 |
Sepúlveda-Crespo, Daniel Diniz, Ana Rita Borrego, Pedro Rodes, Berta Javier de la Mata, Francisco Gómez, Rafael Taveira, Nuno Muñoz-Fernández, Mª Ángeles |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório Comum |
| dc.contributor.author.fl_str_mv |
Briz, Verónica Sepúlveda-Crespo, Daniel Diniz, Ana Rita Borrego, Pedro Rodes, Berta Javier de la Mata, Francisco Gómez, Rafael Taveira, Nuno Muñoz-Fernández, Mª Ángeles |
| dc.subject.por.fl_str_mv |
HIV-2 prevention In vivo mice Microbicides Mode of action Polyanionic carbosilane dendrimers |
| topic |
HIV-2 prevention In vivo mice Microbicides Mode of action Polyanionic carbosilane dendrimers |
| description |
This is the author’s version of a work that was accepted for publication in Nanoscale. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-07-01T00:00:00Z 2015-07-01T00:00:00Z 2016-10-12T08:53:14Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.26/15083 |
| url |
http://hdl.handle.net/10400.26/15083 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Nanoscale. 2015 Sep 21;7(35):14669-83. doi: 10.1039/c5nr03644e 2040-3372 10.1039/C5NR03644E |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Royal Society of Chemistry |
| publisher.none.fl_str_mv |
Royal Society of Chemistry |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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