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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

HDL-Chitosan Nanoparticles for siRNA Delivery as an SR-B1 Receptor Targeted System

Author(s): Rasim Masimov and Gülay Büyükköroğlu*

Volume 26, Issue 14, 2023

Published on: 10 May, 2023

Page: [2541 - 2553] Pages: 13

DOI: 10.2174/1386207326666230406124524

open access plus

Abstract

Aims: High-Density Lipoprotein (HDL) is a complex structure unique to the human body. ApoA-1 protein is a significant structural/functional protein of HDL and provides a natural interaction with the SR-B1 receptors on the cell membrane. The overexpression of the SR-B1 receptor in the membrane of malignant cells suggests that targeting cancer cells can be possible using HDL. The objective of this study was to prepare HDL-conjugated chitosan nanoparticles containing a genetic material that can be used for liver cancer.

Methods: HDL used in the preparation of the formulations have been obtained by isolating from blood samples taken from healthy volunteers. Bcl-2 siRNA inhibiting BCL-2 oncogene was selected as the genetic material. Chitosan nanoparticles were prepared using the ionic gelation method utilizing low molecular weight chitosan. Physicochemical properties of formulations, transfection efficacy, and cytotoxicity of them on 3T3 and HepG2 cell lines were examined.

Results: The average diameters of the selected formulations were below 250 nm with a positive zeta potential value between +36 ± 0.1 and +34 ± 0.5 mV. All formulations protected Bcl-2 siRNA from enzymatic degradation in the presence of serum. Cellular uptake ratios of particles by HepG2 cells were found to be between 76% and 98%. HDL/chitosan nanoparticles/Bcl-2 siRNA complex was found to be more toxic when compared to chitosan nanoparticles/Bcl-2 siRNA complex and naked Bcl-2 siRNA.

Conclusion: According to attained results, the HDL-conjugated chitosan nanoparticles can bring advantages for targeted siRNA delivery to malignant cells that overexpress SR-B1 receptors, such as HepG2.

Keywords: HDL, SR-B1 receptor and ApoA-1, silencing gene-Bcl-2 siRNA, chitosan nanoparticles, antisense technology-gene delivery, targeting therapy-liver cancer.

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