Recent advances in delivering RNA-based therapeutics to mitochondria

Yamada, Yuma; Ishizuka, Sen; Arai, Manae; Maruyama, Minako; Harashima, Hideyoshi

doi:10.1080/14712598.2022.2070427

Cited by 5 publications

(1 citation statement)

References 88 publications

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“…We previously developed a MITO-Porter, an LNP for delivering cargoes to mitochondria. The MITO-Porter could be used to successfully deliver various cargoes including low-molecular-weight compounds and macromolecular compounds to a variety of targets [ 9 , 10 , 11 , 12 ]. This paper describes the encapsulation of BBR in a MITO-Porter that had been modified with octa-arginine (R8) (R8-MITO-Porter (BBR)).…”

Section: Introductionmentioning

confidence: 99%

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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