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Título: | Active targeting of CD4+T lymphocytes by PEI-capped, peptide-functionalized gold nanoparticles |
Autor: | Ncobeni, Nomfundo; de la Torre, Beatriz G.; Albericio, Fernando CSIC ORCID; Kruger, Hendrik G.; Parboosing, Raveen | Palabras clave: | Uptake HIV Active targeting Anti-CD4 peptide Gold nanoparticle |
Fecha de publicación: | 11-jul-2022 | Editor: | IOP Publishing | Citación: | Nanotechnology 33: 405101 (2022) | Resumen: | Active targeting is a promising approach for the treatment of viral infections. In particular, site-specific formulations for the treatment of HIV infection may overcome challenges associated with current ARV regimens. In this study we explored active targeting by synthesizing a gold nanoparticle construct decorated with an anti-CD4 cyclic peptide. The aim was to demonstrate selectivity of the system for the CD4 receptor and to deliver the RNA payload into T-lymphocytes. Colloidal gold nanoparticles functionalized withN-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) were formed by a one-pot synthesis method where thiol modified polyethyleneimine (PEI) was mixed with chloroauric acid. PEI-SPDP AuNPs (gold nanoparticles) were conjugated to an anti-CD4 peptide and loaded with RNA. We measured toxicity and uptake using TZM-bl and HeLa cells. Our findings show that the nanoparticles bind selectively to CD4 + cells. UV-vis characterisation of the nanoparticles revealed a surface plasmon resonance (SPR) peak at 527 nm, corresponding to a 6 nm diameter. HRTEM of the complete nanoparticles visualised circular shaped particles with average diameter of ∼7 nm. The polydispersity index was calculated to be 0.08, indicating monodispersity of complete NPS in solution. Through the pyridine-2-thione assay each nanoparticle was calculated to carry 1.37 × 105SPDP molecules available for peptide binding. Flow cytometry showed that 13.6% of TZM-bl cells, and 0.14% of HeLa cells retained fluorescence after an overnight incubation, an indication of system binding. No internal RNA delivery was demonstrated. Further work is required to improve internalization. | Versión del editor: | 10.1088/1361-6528/ac7885 | URI: | http://hdl.handle.net/10261/310435 | DOI: | 10.1088/1361-6528/ac7885 | ISSN: | 09574484 |
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