Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles

Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles Tina Sepasi Department of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0002-0132-9241 Farhad Bani Department of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Reza Rahbarghazi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Applied Cell Sciences, Advanced Faculty of Medical Sciences, Tabriz University of Medical, Tabriz, Iran Abbas Ebrahimi-Kalan Department of Neuroscience and Cognitive, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad-Reza Sadeghi Department of Molecular Medicine, Advanced Faculty of Medical Sciences, Tabriz University of Medical, Tabriz, Iran Seyedeh Zahra Alamolhoda Department of Medical Biotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Amir Zarebkohan Department of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0002-0186-3516 Tahereh Ghadiri Department of Neuroscience and Cognitive, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, P. R. China

Introduction: Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). Methods: Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy. Results: Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. Conclusion: Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).
05 28 2022 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2021-06-03 2021-10-03 2022-05-28 10.34172/bi.2022.23876 20221103111907 https://bi.tbzmed.ac.ir/Inpress/bi-23876 https://bi.tbzmed.ac.ir/Inpress/bi-23876.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23876.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23876.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23876.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23876.pdf