Dépôt numérique
RECHERCHER

Cytotoxicity assessment, inflammatory properties, and cellular uptake of Neutraplex lipid-based nanoparticles in THP-1 monocyte-derived macrophages

Téléchargements

Téléchargements par mois depuis la dernière année

Plus de statistiques...

Berger, Éric; Breznan, Dalibor; Stals, Sandra; Jasinghe, Viraj J.; Gonçalves, David; Girard, Denis; Faucher, Sylvie; Vincent, Renaud; Thierry, Alain R.; Lavigne, Carole (2017). Cytotoxicity assessment, inflammatory properties, and cellular uptake of Neutraplex lipid-based nanoparticles in THP-1 monocyte-derived macrophages Nanobiomedicine , vol. 4 . p. 1-14. DOI: 10.1177/1849543517746259.

[img]
Prévisualisation
PDF - Version publiée
Disponible sous licence Creative Commons Attribution.

Télécharger (631kB) | Prévisualisation

Résumé

Current antiretroviral drugs used to prevent or treat human immunodeficiency virus type 1 (HIV-1) infection are not able to eliminate the virus within tissues or cells where HIV establishes reservoirs. Hence, there is an urgent need to develop targeted delivery systems to enhance drug concentrations in these viral sanctuary sites. Macrophages are key players in HIV infection and contribute significantly to the cellular reservoirs of HIV because the virus can survive for prolonged periods in these cells. In the present work, we investigated the potential of the lipid-based Neutraplex nanosystem to deliver anti-HIV therapeutics in human macrophages using the human monocyte/macrophage cell line THP-1. Neutraplex nanoparticles as well as cationic and anionic Neutraplex nanolipoplexes (Neutraplex/small interfering RNA) were prepared and characterized by dynamic light scattering. Neutraplex nanoparticles showed low cytotoxicity in CellTiter-Blue reduction and lactate dehydrogenase release assays and were not found to have pro-inflammatory effects. In addition, confocal studies showed that the Neutraplex nanoparticles and nanolipoplexes are rapidly internalized into THP-1 macrophages and that they can escape the late endosome/lysosome compartment allowing the delivery of small interfering RNAs in the cytoplasm. Furthermore, HIV replication was inhibited in the in vitro TZM-bl infectivity assay when small interfering RNAs targeting CXCR4 co-receptor was delivered by Neutraplex nanoparticles compared to a random small interfering RNA sequence. This study demonstrates that the Neutraplex nanosystem has potential for further development as a delivery strategy to efficiently and safely enhance the transport of therapeutic molecules into human monocyte-derived macrophages in the aim of targeting HIV-1 in this cellular reservoir. © The Author(s) 2017.

Type de document: Article
Mots-clés libres: drug delivery nanosystem; HIV; Nanomedicine; siRNA; THP-1
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 21 mars 2019 15:58
Dernière modification: 21 mars 2019 15:58
URI: http://espace.inrs.ca/id/eprint/6703

Actions (Identification requise)

Modifier la notice Modifier la notice