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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Construction of GPC3-modified Lipopolymer SiRNA Delivery System

Author(s): Dandan Sun, Xiaoyu Li, Yaru Liu, Jishan Quan* and Guangyu Jin*

Volume 30, Issue 19, 2024

Published on: 19 April, 2024

Page: [1507 - 1518] Pages: 12

DOI: 10.2174/0113816128258852231204102044

Price: $65

Abstract

Background: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared.

Methods: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining.

Results: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation.

Conclusion: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

Keywords: GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), gene carrier, transfection efficiency, gene therapy, therapeutic mechanism, hepatocellular carcinoma.

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