Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles
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. T...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2023-03-01
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| Series: | BioImpacts |
| Subjects: | |
| Online Access: | https://bi.tbzmed.ac.ir/PDF/bi-13-133.pdf |
| _version_ | 1797846185570992128 |
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| author | Tina Sepasi Farhad Bani Reza Rahbarghazi Abbas Ebrahimi-Kalan Mohammad-Reza Sadeghi Seyedeh Zahra Alamolhoda Amir Zarebkohan Tahereh Ghadiri Huile Gao |
| author_facet | Tina Sepasi Farhad Bani Reza Rahbarghazi Abbas Ebrahimi-Kalan Mohammad-Reza Sadeghi Seyedeh Zahra Alamolhoda Amir Zarebkohan Tahereh Ghadiri Huile Gao |
| author_sort | Tina Sepasi |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-04-09T17:50:49Z |
| format | Article |
| id | doaj.art-d0dc7c960343469b8c2cc1bb48b8494c |
| institution | Directory Open Access Journal |
| issn | 2228-5660 2228-5652 |
| language | English |
| last_indexed | 2024-04-09T17:50:49Z |
| publishDate | 2023-03-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | BioImpacts |
| spelling | doaj.art-d0dc7c960343469b8c2cc1bb48b8494c2023-04-16T06:59:08ZengTabriz University of Medical SciencesBioImpacts2228-56602228-56522023-03-0113213314410.34172/bi.2022.23876bi-23876Targeted gene delivery to the brain using CDX-modified chitosan nanoparticlesTina Sepasi0Farhad Bani1Reza Rahbarghazi2Abbas Ebrahimi-Kalan3Mohammad-Reza Sadeghi4Seyedeh Zahra Alamolhoda5Amir Zarebkohan6Tahereh Ghadiri7Huile Gao8Department of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Neuroscience and Cognitive, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Molecular Medicine, Advanced Faculty of Medical Sciences, Tabriz University of Medical, Tabriz, IranDepartment of Medical Biotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Medical Nanotechnology, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Neuroscience and Cognitive, Advanced Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranKey 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. ChinaIntroduction: 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).https://bi.tbzmed.ac.ir/PDF/bi-13-133.pdftargeted gene deliverybraincdxchitosannanoparticles |
| spellingShingle | Tina Sepasi Farhad Bani Reza Rahbarghazi Abbas Ebrahimi-Kalan Mohammad-Reza Sadeghi Seyedeh Zahra Alamolhoda Amir Zarebkohan Tahereh Ghadiri Huile Gao Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles BioImpacts targeted gene delivery brain cdx chitosan nanoparticles |
| title | Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles |
| title_full | Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles |
| title_fullStr | Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles |
| title_full_unstemmed | Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles |
| title_short | Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles |
| title_sort | targeted gene delivery to the brain using cdx modified chitosan nanoparticles |
| topic | targeted gene delivery brain cdx chitosan nanoparticles |
| url | https://bi.tbzmed.ac.ir/PDF/bi-13-133.pdf |
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