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

Autor: Tina Sepasi, Farhad Bani, Reza Rahbarghazi, Abbas Ebrahimi-Kalan, Mohammad-Reza Sadeghi, Seyedeh Zahra Alamolhoda, Amir Zarebkohan, Tahereh Ghadiri, Huile Gao
Rok vydání: 2022
Předmět:
Zdroj: BioImpacts.
ISSN: 2228-5652
2228-5660
DOI: 10.34172/bi.2022.23876
Popis: 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).
Databáze: OpenAIRE
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