Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases and a major contributor to dementia. Although the cause of this condition has been identified long ago as aberrant aggregations of amyloid and tau proteins, effective therapies for it remain elusive. The complexities of...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14954 |
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| author | Moonseok Choi Junghwa Ryu Huy Duc Vu Dongsoo Kim Young-Jin Youn Min Hui Park Phuong Tu Huynh Gyu-Bin Hwang Sung Won Youn Yun Ha Jeong |
| author_facet | Moonseok Choi Junghwa Ryu Huy Duc Vu Dongsoo Kim Young-Jin Youn Min Hui Park Phuong Tu Huynh Gyu-Bin Hwang Sung Won Youn Yun Ha Jeong |
| author_sort | Moonseok Choi |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases and a major contributor to dementia. Although the cause of this condition has been identified long ago as aberrant aggregations of amyloid and tau proteins, effective therapies for it remain elusive. The complexities of drug development for AD treatment are often compounded by the impermeable blood–brain barrier and low-yield brain delivery. In addition, the use of high drug concentrations to overcome this challenge may entail side effects. To address these challenges and enhance the precision of delivery into brain regions affected by amyloid aggregation, we proposed a transferrin-conjugated nanoparticle-based drug delivery system. The transferrin-conjugated melittin-loaded L-arginine-coated iron oxide nanoparticles (Tf-MeLioNs) developed in this study successfully mitigated melittin-induced cytotoxicity and hemolysis in the cell culture system. In the 5XFAD mouse brain, Tf-MeLioNs remarkably reduced amyloid plaque accumulation, particularly in the hippocampus. This study suggested Tf-LioNs as a potential drug delivery platform and Tf-MeLioNs as a candidate for therapeutic drug targeting of amyloid plaques in AD. These findings provide a foundation for further exploration and advancement in AD therapeutics. |
| first_indexed | 2024-03-10T21:42:45Z |
| format | Article |
| id | doaj.art-6ff1843d9e6e4fb79cd9381eeb749786 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:42:45Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6ff1843d9e6e4fb79cd9381eeb7497862023-11-19T14:33:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124191495410.3390/ijms241914954Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse BrainMoonseok Choi0Junghwa Ryu1Huy Duc Vu2Dongsoo Kim3Young-Jin Youn4Min Hui Park5Phuong Tu Huynh6Gyu-Bin Hwang7Sung Won Youn8Yun Ha Jeong9Department of Neurodegenerative Diseases Research Group, Korea Brain Research Institute, 61, Cheomdan ro, Dong gu, Daegu 41062, Republic of KoreaDepartment of Radiology, School of Medicine, Daegu Catholic University, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of KoreaDepartment of Radiology, School of Medicine, Daegu Catholic University, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of KoreaDepartment of Neurodegenerative Diseases Research Group, Korea Brain Research Institute, 61, Cheomdan ro, Dong gu, Daegu 41062, Republic of KoreaDepartment of Neurodegenerative Diseases Research Group, Korea Brain Research Institute, 61, Cheomdan ro, Dong gu, Daegu 41062, Republic of KoreaDepartment of Radiology, School of Medicine, Daegu Catholic University, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of KoreaDepartment of Radiology, School of Medicine, Daegu Catholic University, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of KoreaDepartment of Neurodegenerative Diseases Research Group, Korea Brain Research Institute, 61, Cheomdan ro, Dong gu, Daegu 41062, Republic of KoreaDepartment of Radiology, School of Medicine, Daegu Catholic University, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of KoreaDepartment of Neurodegenerative Diseases Research Group, Korea Brain Research Institute, 61, Cheomdan ro, Dong gu, Daegu 41062, Republic of KoreaAlzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases and a major contributor to dementia. Although the cause of this condition has been identified long ago as aberrant aggregations of amyloid and tau proteins, effective therapies for it remain elusive. The complexities of drug development for AD treatment are often compounded by the impermeable blood–brain barrier and low-yield brain delivery. In addition, the use of high drug concentrations to overcome this challenge may entail side effects. To address these challenges and enhance the precision of delivery into brain regions affected by amyloid aggregation, we proposed a transferrin-conjugated nanoparticle-based drug delivery system. The transferrin-conjugated melittin-loaded L-arginine-coated iron oxide nanoparticles (Tf-MeLioNs) developed in this study successfully mitigated melittin-induced cytotoxicity and hemolysis in the cell culture system. In the 5XFAD mouse brain, Tf-MeLioNs remarkably reduced amyloid plaque accumulation, particularly in the hippocampus. This study suggested Tf-LioNs as a potential drug delivery platform and Tf-MeLioNs as a candidate for therapeutic drug targeting of amyloid plaques in AD. These findings provide a foundation for further exploration and advancement in AD therapeutics.https://www.mdpi.com/1422-0067/24/19/14954Alzheimer’s diseasenanoparticlemelittiniron oxidetransferrinamyloid plaque |
| spellingShingle | Moonseok Choi Junghwa Ryu Huy Duc Vu Dongsoo Kim Young-Jin Youn Min Hui Park Phuong Tu Huynh Gyu-Bin Hwang Sung Won Youn Yun Ha Jeong Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain International Journal of Molecular Sciences Alzheimer’s disease nanoparticle melittin iron oxide transferrin amyloid plaque |
| title | Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain |
| title_full | Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain |
| title_fullStr | Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain |
| title_full_unstemmed | Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain |
| title_short | Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain |
| title_sort | transferrin conjugated melittin loaded l arginine coated iron oxide nanoparticles for mitigating beta amyloid pathology of the 5xfad mouse brain |
| topic | Alzheimer’s disease nanoparticle melittin iron oxide transferrin amyloid plaque |
| url | https://www.mdpi.com/1422-0067/24/19/14954 |
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