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Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine

Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation...

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Autores principales: Hori, Ikuma, Harashima, Hideyoshi, Yamada, Yuma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863876/
https://www.ncbi.nlm.nih.gov/pubmed/36674418
http://dx.doi.org/10.3390/ijms24020903
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author Hori, Ikuma
Harashima, Hideyoshi
Yamada, Yuma
author_facet Hori, Ikuma
Harashima, Hideyoshi
Yamada, Yuma
author_sort Hori, Ikuma
collection PubMed
description Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation of intracellular metabolism. Therefore, BBR has attracted considerable interest as a possible therapeutic drug for neurodegenerative diseases. While BBR has been reported to act on mitochondria, there are few reports on the efficient delivery of BBR into mitochondria. This paper reports on the mitochondrial delivery of BBR using a lipid nanoparticle (LNP), a “MITO-Porter” that targets mitochondria, and its pharmacological action in Neuro2a cells, a model neuroblastoma. A MITO-Porter containing encapsulated BBR (MITO-Porter (BBR)) was prepared. Treatment with MITO-Porter (BBR) increased the amount of BBR that accumulated in mitochondria compared with a treatment with naked BBR. Treatment with MITO-Porter (BBR) resulted in increased ATP production in Neuro2a cells, which are important for maintaining life phenomena, compared with treatment with naked BBR. Treatment with MITO-Porter (BBR) also increased the level of expression of mitochondrial ubiquitin ligase (MITOL), which is involved in mitochondrial quality control. Our findings indicate that increasing the accumulation of BBR into mitochondria is important for inducing enhanced pharmacological actions. The use of this system has the potential for being important in terms of the regulation of the metabolic mechanism of mitochondria in nerve cells.
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spelling pubmed-98638762023-01-22 Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine Hori, Ikuma Harashima, Hideyoshi Yamada, Yuma Int J Mol Sci Article Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation of intracellular metabolism. Therefore, BBR has attracted considerable interest as a possible therapeutic drug for neurodegenerative diseases. While BBR has been reported to act on mitochondria, there are few reports on the efficient delivery of BBR into mitochondria. This paper reports on the mitochondrial delivery of BBR using a lipid nanoparticle (LNP), a “MITO-Porter” that targets mitochondria, and its pharmacological action in Neuro2a cells, a model neuroblastoma. A MITO-Porter containing encapsulated BBR (MITO-Porter (BBR)) was prepared. Treatment with MITO-Porter (BBR) increased the amount of BBR that accumulated in mitochondria compared with a treatment with naked BBR. Treatment with MITO-Porter (BBR) resulted in increased ATP production in Neuro2a cells, which are important for maintaining life phenomena, compared with treatment with naked BBR. Treatment with MITO-Porter (BBR) also increased the level of expression of mitochondrial ubiquitin ligase (MITOL), which is involved in mitochondrial quality control. Our findings indicate that increasing the accumulation of BBR into mitochondria is important for inducing enhanced pharmacological actions. The use of this system has the potential for being important in terms of the regulation of the metabolic mechanism of mitochondria in nerve cells. MDPI 2023-01-04 /pmc/articles/PMC9863876/ /pubmed/36674418 http://dx.doi.org/10.3390/ijms24020903 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hori, Ikuma
Harashima, Hideyoshi
Yamada, Yuma
Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title_full Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title_fullStr Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title_full_unstemmed Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title_short Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
title_sort development of a mitochondrial targeting lipid nanoparticle encapsulating berberine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863876/
https://www.ncbi.nlm.nih.gov/pubmed/36674418
http://dx.doi.org/10.3390/ijms24020903
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