Issue 19, 2018

Sulfonate-ended carbosilane dendrimers with a flexible scaffold cause inactivation of HIV-1 virions and gp120 shedding

Abstract

Infection with human immunodeficiency virus type 1 (HIV-1) continues to be a global public health issue, especially in low-resource countries. Sexual transmission is responsible for the majority of HIV-1 infections worldwide. Women are more susceptible to HIV-1 acquisition than men and represent nearly 50% of the HIV-infected population. Topical vaginal microbicides that act at the earlier stages of infection offer a prevention strategy to reduce the acquisition of HIV-1. Dendrimers are nano-sized, radially symmetric molecules with a well-defined and monodisperse structure consisting of tree-like arms or branches. We perform a TZM.bl cell line-based screening of two families of carbosilane dendrimers (6 nanocompounds: G1-S12P, G2-S24P, G3-S48P, G1-C12P, G2-C24P and G3-C48P) that we have previously synthesized, containing 12, 24 or 48 sulfonate (or carboxylate) end-groups and a polyphenolic core. This work shows that second- and third-generation sulfonate-ended carbosilane dendrimers with a polyphenolic core (G2-S24P and G3-S48P, respectively) display low cytotoxicity (CC50 > 300 μM) with virucidal anti-R5-HIV-1 activity (EC50 < 50 nM; therapeutic index >6000) causing irreversible HIV-1 inactivation (80–90%) by loss of HIV-1 RNA (40%), gp120 shedding (70–80%) and p24 capsid protein release (45–60%). Herein, we demonstrate that sulfonate end-groups and a flexible scaffold from carbosilane dendrimers strongly influence their properties acting as potent virucides.

Graphical abstract: Sulfonate-ended carbosilane dendrimers with a flexible scaffold cause inactivation of HIV-1 virions and gp120 shedding

Supplementary files

Article information

Article type
Paper
Submitted
27 Feb 2018
Accepted
07 Eph 2018
First published
09 Eph 2018

Nanoscale, 2018,10, 8998-9011

Sulfonate-ended carbosilane dendrimers with a flexible scaffold cause inactivation of HIV-1 virions and gp120 shedding

D. Sepúlveda-Crespo, F. J. de la Mata, R. Gómez and M. A. Muñoz-Fernández, Nanoscale, 2018, 10, 8998 DOI: 10.1039/C8NR01664J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements