Lactosylated lipid calcium phosphate-based nanoparticles: A promising approach for efficient DNA delivery to hepatocytes

Document Type : Original Article

Authors

1 Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

4 Applied Biomedical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

5 Targeted Drug Delivery Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

10.22038/ijbms.2024.76683.16602

Abstract

Objective(s): For safe and effective gene therapy, the ability to deliver the therapeutic nucleic acid to the target sites is crucial. In this study, lactosylated lipid phosphate calcium nanoparticles (lac-LCP) were developed for targeted delivery of pDNA to the hepatocyte cells. The lac-LCP formulation contained lactose-modified cholesterol (CHL), a ligand that binds to the asialoglycoprotein receptor (ASGR) expressed on hepatocytes, and polyethyleneimine (PEI) in the core.  
Materials and Methods: Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) were used to monitor the chemical modification, and the physicochemical properties of NPs were studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). To evaluate transfection efficiency, cellular uptake and GFP expression were assessed using fluorescence microscopy and flow cytometry. 
Results: The results revealed that lactose-targeted particles (lac-LCP) had a significant increase in cellular uptake by hepatocytes. The inclusion of a low molecular weight PEI (1.8 KDa) with a low PEI/pDNA ratio of 1 in the core of LCP, elicited high degrees of GFP protein expression (by 5 and 6-fold), which exhibited significantly higher efficiency than PEI 1.8 KDa and Lipofectamine. 
Conclusion: The successful functionalization and nuclear delivery of LCP NPs described here indicate its promise as an efficient delivery vector to hepatocyte nuclei. 

Keywords

Main Subjects

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 09 April 2024

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