Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile

Chonco, Louis; Pion, Marjorie; Vacas, E.; Rasines, Beatriz; Malý, Marek; Serramía, Ma Jesús; López-Fernández, Luis Andrés; Mata, F. Javier de la; Álvarez, Susana; Gómez, Rafael; Muñoz‐Fernández, María Ángeles

doi:10.1016/j.jconrel.2012.04.050

Cited by 80 publications

(103 citation statements)

References 54 publications

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“…8,9,14,15 Eight dendrimers were dissolved in distilled water in a final concentration of 1 mM. Dilutions to µM range were generated in distilled water from the stock.…”

Section: Materials and Methods Compoundsmentioning

confidence: 99%

“…7,8,14 They are distinguished from other dendrimers in their high apolarity of central core and high mobility of peripheral branches, features that turn them into outstanding candidates to be used in biomedical applications. Carbosilane dendrimers were effective to inhibit HIV infection and transmission within genital mucosa and were safe in mice models.…”

Section: Introductionmentioning

confidence: 99%

“…Carbosilane dendrimers were effective to inhibit HIV infection and transmission within genital mucosa and were safe in mice models. 7,8,14 Thus, potent antiviral activity of these nanosystems against other sexually transmitted pathogens, such as HSV-2, could be extremely important in order to develop broad-spectrum effective microbicides.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

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Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH–gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.

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“…8,9,14,15 Eight dendrimers were dissolved in distilled water in a final concentration of 1 mM. Dilutions to µM range were generated in distilled water from the stock.…”

Section: Materials and Methods Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…[8][9][10] In the last few years, nanotechnology offered a huge battery of novel nanoparticles such as dendrimers and macromolecules characterized by hyperbranched, well-defined, monodisperse, three-dimensional structures that are being developed as drug delivery vehicles or as therapeutic agents. [11][12][13][14][15][16][17] The controlled synthesis of dendrimers allows the assembly of highly defined, single molecule structures that radiate out in branches from a central initiator core. The type of core and branching units can be engineered to generate a broad variety of dendrimers with different sizes, shapes, and surface chemical functionalized groups that can provide distinct biological and pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

“…23 A relative recent group of dendrimers with carbosilane structure has also demonstrated its potential as topical microbicides against HIV and other pathogens. 12,13,[24][25][26][27][28][29] These nanosystems present a C-and Si-based skeleton, and they distinguish from other dendrimers in the high apolarity of their central core and the high mobility of their peripheral branches.…”

Section: Introductionmentioning

confidence: 99%

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

Vacas-Córdoba¹,

Malý²,

Mata³

et al. 2016

IJN

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Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection.

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Inorganic Dendrimers and Their Applications

Caminade

2019

Smart Inorganic Polymers

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Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile

Cited by 80 publications

References 54 publications

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

Inorganic Dendrimers and Their Applications

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