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South African Journal of Chemistry

On-line version ISSN 1996-840X
Print version ISSN 0379-4350

Abstract

PARBOOSING, Raveen; GOVENDER, Thavendran; MAGUIRE, Glenn E.M.  and  KRUGER, Hendrik G.. Synthesis, Characterization and Biocompatibility of a Multifunctional Gold Nanoparticle System for the Delivery of Single-Stranded RNA to Lymphocytes. S.Afr.j.chem. (Online) [online]. 2018, vol.71, pp.1-14. ISSN 1996-840X.  http://dx.doi.org/10.17159/0379-4350/2018/v71a1.

The use of RNA macromolecules as therapeutic agents for HIV and other infectious diseases is promising but limited by suboptimal delivery to the target site. With HIV infection, this is particularly challenging since lymphocytes are particularly difficult to transfect. This paper describes an innovative strategy for the intracellular delivery of a novel single-stranded RNA (oligoribonucleotide) with putative anti-HIV activity. This strategy is based on a PEGylated gold nanoparticle scaffold covalently linked to the thiol-modified oligoribonucleotide via a cleavable N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) linker molecule. The nanoparticle was then coated with a cationic polymer (polyethyleneimine) to facilitate cell entry and endosomal escape. A synthetic anti-CD4 cyclic targeting peptide was attached to the polyethyleneimine-coated nanoparticle via an SPDP linker molecule, in an attempt to enhance uptake and selectivity. Synthesis, characterization, SPDP and RNA loading, cytotoxicity and antiviral activity of the nanoparticle are described. Approximately 45 000 strands of RNA were taken up per lymphocyte. Uptake was limited by relatively inefficient loading of RNA onto the gold nanoparticle surface (1 strand per 4.8 nm2 of nanoparticle surface area) and significant aggregation of the nanoparticle in physiological solutions. No antiviral activity was demonstrated, possibly due to insufficient intracytoplasmic delivery of the RNA.

Keywords : Gold nanoparticle; polyethyleneimine; transfection; RNA delivery.

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