Development of a T Cell-targeted siRNA Delivery System Against HIV-1 Using Modified Superparamagnetic Iron Oxide Nanoparticles: An In Vitro Study

In spite of the promising properties of small interfering RNAs (siRNAs) in the treatment of infectious diseases, safe and efficient siRNA delivery to target cells is still a challenge. In this research, an effective siRNA delivery approach (against HIV-1) has been reported using targeted modified su...

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Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 111; no. 5; p. 1463
Main Authors:	Kamalzare, Sara, Iranpur Mobarakeh, Vahid, Mirzazadeh Tekie, Farnaz Sadat, Hajiramezanali, Maliheh, Riazi-Rad, Farhad, Yoosefi, Sepideh, Normohammadi, Zahra, Irani, Shiva, Tavakoli, Mohamadreza, Rahimi, Pooneh, Atyabi, Fatemeh
Format:	Journal Article
Language:	English
Published:	United States 01-05-2022
Subjects:	Chitosan - chemistry HIV-1 - genetics Magnetic Iron Oxide Nanoparticles Magnetite Nanoparticles - chemistry Nanoparticles - chemistry RNA, Small Interfering - genetics T-Lymphocytes siRNA delivery HIV-1 nef CD4 SPION
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Summary:	In spite of the promising properties of small interfering RNAs (siRNAs) in the treatment of infectious diseases, safe and efficient siRNA delivery to target cells is still a challenge. In this research, an effective siRNA delivery approach (against HIV-1) has been reported using targeted modified superparamagnetic iron oxide nanoparticles (SPIONs). Trimethyl chitosan-coated SPION (TMC-SPION) containing siRNA was synthesized and chemically conjugated to a CD4-specific monoclonal antibody (as a targeting moiety). The prepared nanoparticles exhibited a high siRNA loading efficiency with a diameter of about 85 nm and a zeta potential of +28 mV. The results of the cell viability assay revealed the low cytotoxicity of the optimized nanoparticles. The cellular delivery of the targeted nanoparticles (into T cells) and the gene silencing efficiency of the nanoparticles (containing anti-nef siRNA) were dramatically improved compared to those of nontargeted nanoparticles. In conclusion, this study offers a promising targeted delivery platform to induce gene silencing in target cells. Our approach may find potential use in the design of effective vehicles for many therapeutic applications, particularly for HIV treatment.
ISSN:	1520-6017
DOI:	10.1016/j.xphs.2021.10.018