Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology
Abstract Recently, oligonucleotide post-transcriptional gene silencing, antisense oligonucleotides, small interfering RNA, ribozymes, and Deoxyribozymes (DNAzymes) have been used to tackle neurodegenerative diseases such as Alzheimer’s and polyglutamine diseases like Huntington’s disease. However, t...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-04433-2 |
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| author | Mohammad Javad Hoseinifar Faranak Aghaz Zahra Asadi Peyman Asadi Seyed Ershad Nedaei Elham Arkan Ali Pourmotabbed Gholamreza Bahrami Tayebeh Pourmotabbed |
| author_facet | Mohammad Javad Hoseinifar Faranak Aghaz Zahra Asadi Peyman Asadi Seyed Ershad Nedaei Elham Arkan Ali Pourmotabbed Gholamreza Bahrami Tayebeh Pourmotabbed |
| author_sort | Mohammad Javad Hoseinifar |
| collection | DOAJ |
| description | Abstract Recently, oligonucleotide post-transcriptional gene silencing, antisense oligonucleotides, small interfering RNA, ribozymes, and Deoxyribozymes (DNAzymes) have been used to tackle neurodegenerative diseases such as Alzheimer’s and polyglutamine diseases like Huntington’s disease. However, the primary obstacle to the therapeutic effectiveness of these oligonucleotides is the blood-brain barrier (BBB), a crucial protective mechanism limiting drug penetration into brain cells. In this study, we generated a DNAzyme-loaded nanoliposome (DNZ-NLP) as a drug delivery system to effectively deliver and release the DNAzymes to the brain. The investigation of physicochemical characteristics of fabricated nanoliposomes, particularly size, morphology, and surface charge, revealed that the size of DNZ-NLPs was ~ 68 nm, an optimum size for brain delivery. Cellular uptake and cytocompatibility studies using SH-SY5Y human neuroblastoma cells demonstrated that both blank nanoliposomes (B-NLPs) and DNZ-NLPs were cytocompatible, and DNZ-NLPs had a stable biphasic release profile in 48 h. Most importantly, about 60% of intravenously administered DNZ-NLPs to the healthy mouse were found in the brains of the animals. These findings confirmed that DNZ-NLPs passed the BBB. The controlled release of DNAzymes, the maximal cytocompatibility, and significantly improved BBB permeability suggest that our DNZ-NLPs offer a promising formulation for delivering all types of oligonucleotides to the brain for neurodegenerative disease treatments. |
| format | Article |
| id | doaj-art-a50876552cc740ec92cb508e1c7070e4 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a50876552cc740ec92cb508e1c7070e42025-08-20T03:16:31ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-04433-2Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technologyMohammad Javad Hoseinifar0Faranak Aghaz1Zahra Asadi2Peyman Asadi3Seyed Ershad Nedaei4Elham Arkan5Ali Pourmotabbed6Gholamreza Bahrami7Tayebeh Pourmotabbed8Nano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical SciencesNano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical SciencesStudents Research Committee, Kermanshah University of Medical SciencesNano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical SciencesDepartment of Physiology, School of Medicine, Kermanshah University of Medical SciencesNano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical SciencesDepartment of Physiology, School of Medicine, Kermanshah University of Medical SciencesMedical Biology Research Center, Health Technology Institute, Kermanshah University of Medical SciencesDepartment of Microbiology, Immunology, and Biochemistry, Health Science Center, University of TennesseeAbstract Recently, oligonucleotide post-transcriptional gene silencing, antisense oligonucleotides, small interfering RNA, ribozymes, and Deoxyribozymes (DNAzymes) have been used to tackle neurodegenerative diseases such as Alzheimer’s and polyglutamine diseases like Huntington’s disease. However, the primary obstacle to the therapeutic effectiveness of these oligonucleotides is the blood-brain barrier (BBB), a crucial protective mechanism limiting drug penetration into brain cells. In this study, we generated a DNAzyme-loaded nanoliposome (DNZ-NLP) as a drug delivery system to effectively deliver and release the DNAzymes to the brain. The investigation of physicochemical characteristics of fabricated nanoliposomes, particularly size, morphology, and surface charge, revealed that the size of DNZ-NLPs was ~ 68 nm, an optimum size for brain delivery. Cellular uptake and cytocompatibility studies using SH-SY5Y human neuroblastoma cells demonstrated that both blank nanoliposomes (B-NLPs) and DNZ-NLPs were cytocompatible, and DNZ-NLPs had a stable biphasic release profile in 48 h. Most importantly, about 60% of intravenously administered DNZ-NLPs to the healthy mouse were found in the brains of the animals. These findings confirmed that DNZ-NLPs passed the BBB. The controlled release of DNAzymes, the maximal cytocompatibility, and significantly improved BBB permeability suggest that our DNZ-NLPs offer a promising formulation for delivering all types of oligonucleotides to the brain for neurodegenerative disease treatments.https://doi.org/10.1038/s41598-025-04433-2DNAzymeBlood-Brain barrierNanoliposomeBBB permeability |
| spellingShingle | Mohammad Javad Hoseinifar Faranak Aghaz Zahra Asadi Peyman Asadi Seyed Ershad Nedaei Elham Arkan Ali Pourmotabbed Gholamreza Bahrami Tayebeh Pourmotabbed Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology Scientific Reports DNAzyme Blood-Brain barrier Nanoliposome BBB permeability |
| title | Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology |
| title_full | Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology |
| title_fullStr | Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology |
| title_full_unstemmed | Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology |
| title_short | Facilitating DNAzyme transport across the blood-brain barrier with nanoliposome technology |
| title_sort | facilitating dnazyme transport across the blood brain barrier with nanoliposome technology |
| topic | DNAzyme Blood-Brain barrier Nanoliposome BBB permeability |
| url | https://doi.org/10.1038/s41598-025-04433-2 |
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