Validation of the Mitochondrial Delivery of Vitamin B1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

Yamada, Yuma; Ishimaru, Takuya; Ikeda, Kohei; Harashima, Hideyoshi

doi:10.1016/j.xphs.2021.08.033

Cited by 11 publications

(8 citation statements)

References 22 publications

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“…As shown in Figure 3 , treatment with R8-MITO-Porter (BBR) caused an increased accumulation of BBR into Neuro2a cells compared with treatment with the other samples. This result was consistent with previous reports of increased drug delivery via cellular uptake and mitochondrial membrane fusion using a MITO-Porter with R8 on the surface [ 9 , 17 ]. As a consequence of the induced mitochondrial stress response, the amount of the intracellular ATP increased after treatment with R8-MITO-Porter (BBR).…”

Section: Discussionsupporting

confidence: 93%

Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine

Hori¹,

Harashima²,

Yamada³

2023

IJMS

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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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Section: Discussionsupporting

confidence: 93%

Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine

Hori¹,

Harashima²,

Yamada³

2023

IJMS

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“…In our previous report, in vitro experiments using neuroblasts, showed that TPP can be delivered to mitochondria using this MITO‐Porter system and that ATP production is activated as a result 25 . We, therefore, conclude that the MITO‐Porter (TPP) was internalized into neuroblasts in the brain of the BCCAO model to activate ATP production, and likely exerted neuroprotective effects in the brain.…”

Section: Discussionmentioning

confidence: 67%

“…In our previous report, in vitro experiments using neuroblasts, showed that TPP can be delivered to mitochondria using this MITO-Porter system and that ATP production is activated as a result. 25 We, therefore, conclude that the MITO-Porter (TPP) was internalized into neuroblasts in the brain of the BCCAO model to activate ATP production, and likely exerted neuroprotective effects in the brain. Although it was not possible for us to directly evaluate ATP production and PDHC / OGDHC activities in the brain, our findings indicate that the MITO-Porter (TPP) has some potential for use as an innovative therapeutic strategy for the treatment of certain types of brain dysfunctions.…”

Section: Discussionmentioning

confidence: 86%

“…TPP was packaged in the MITO‐Porters using the reverse‐phase evaporation method 25,41 . The lipid compositions of the preparations are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…TPP was packaged in the MITO-Porters using the reversephase evaporation method. 25,41 The lipid compositions of the preparations are shown in Table 1. The lipid suspension employed for the MITO-Porter (TPP) included DOPE, SM.…”

Section: Construction Of the Mito-porter (Tpp)mentioning

confidence: 99%

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Validation of a therapeutic strategy involving the mitochondrial delivery of thiamine pyrophosphate using brain damage induced mouse model

Yamada

Ishimaru

Harashima

2022

Clinical and Translational Dis

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Ischemic brain disease, a type of cerebrovascular disease, has a high mortality rate, and even when patients survive, they are frequently affected by neurological dysfunction due to damage to brain cells. Strategies to increase intracellular adenosine triphosphate (ATP) production are promising approaches for tissue regeneration and restoring neurological function. We report here on an attempt to deliver thiamine pyrophosphate (TPP), a coenzyme that activates the tricarboxylic acid cycle, which is responsible for ATP production, to mitochondria. To achieve this, we used a MITO‐Porter, a liposomal drug delivery system for delivering various cargoes to mitochondria via membrane fusion. In the present study, we investigated the therapeutic effect of the MITO‐Porter (TPP) focusing on its delivery to the brain and neurological function using a bilateral common carotid artery occlusion (BCCAO) mouse model. Fluorescent microscopic analyses confirmed, after a cerebral ischemia‐reperfusion injury had been induced, that the intracerebral delivery of the MITO‐Porter occurred after intravenous administration. Behavioral analyses indicated that the MITO‐Porter (TPP) resulted in significant therapeutic effects compared to the corresponding administration of naked TPP. Histological evaluations also confirmed that the MITO‐Porter (TPP) clearly had an effect on the growth of brain neurons in the BCCAO mouse. Our findings indicate that the mitochondrial delivery of TPP represents a potential innovative therapeutic strategy for enhancing mitochondrial energy production in certain cases of brain diseases.

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Nanomedicine for Maternal and Fetal Health

Carter,

Better,

Abbasi

et al. 2023

Small

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Conception, pregnancy, and childbirth are complex processes that affect both mother and fetus. Thus, it is perhaps not surprising that in the United States alone, roughly 11% of women struggle with infertility and 16% of pregnancies involve some sort of complication. This presents a clear need to develop safe and effective treatment options, though the development of therapeutics for use in women's health and particularly in pregnancy is relatively limited. Physiological and biological changes during the menstrual cycle and pregnancy impact biodistribution, pharmacokinetics, and efficacy, further complicating the process of administration and delivery of therapeutics. In addition to the complex pharmacodynamics, there is also the challenge of overcoming physiological barriers that impact various routes of local and systemic administration, including the blood–follicle barrier and the placenta. Nanomedicine presents a unique opportunity to target and sustain drug delivery to the reproductive tract and other relevant organs in the mother and fetus, as well as improve the safety profile and minimize side effects. Nanomedicine‐based approaches have the potential to improve the management and treatment of infertility, obstetric complications, and fetal conditions.

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Validation of the Mitochondrial Delivery of Vitamin B1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

Cited by 11 publications

References 22 publications

Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine

Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine

Validation of a therapeutic strategy involving the mitochondrial delivery of thiamine pyrophosphate using brain damage induced mouse model

Nanomedicine for Maternal and Fetal Health

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