Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model

Abstract Mitochondrial transfer emerges as a promising therapy for the restoration of mitochondrial function in damaged cells, mainly due to its limited immunogenicity. However, isolated mitochondria rapidly lose function because they produce little energy outside cells. Therefore, this study invest...

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Main Authors: Hui Bang Cho, Hye‐Ryoung Kim, Sujeong Lee, Chae Won Cho, Ji‐In Park, Seulki Youn, Gyuwon So, Sumin Kang, Hye Jin Kim, Keun‐Hong Park
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202415303
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author Hui Bang Cho
Hye‐Ryoung Kim
Sujeong Lee
Chae Won Cho
Ji‐In Park
Seulki Youn
Gyuwon So
Sumin Kang
Hye Jin Kim
Keun‐Hong Park
author_facet Hui Bang Cho
Hye‐Ryoung Kim
Sujeong Lee
Chae Won Cho
Ji‐In Park
Seulki Youn
Gyuwon So
Sumin Kang
Hye Jin Kim
Keun‐Hong Park
author_sort Hui Bang Cho
collection DOAJ
description Abstract Mitochondrial transfer emerges as a promising therapy for the restoration of mitochondrial function in damaged cells, mainly due to its limited immunogenicity. However, isolated mitochondria rapidly lose function because they produce little energy outside cells. Therefore, this study investigates whether near infrared (NIR)‐mediated nicotinamide adenine dinucleotide (NADH) pre‐treatment enhances mitochondrial function and stability in mitochondria‐donor cells prior to transplantation. Clinical applications of NADH, an essential electron donor in the oxidative phosphorylation process, are restricted due to the limited cellular uptake of NADH. To address this, a photo‐mediated method optimizes direct NADH delivery into cells and increases NADH absorption. L6 cells treated with NADH and irradiated with NIR enhanced NADH uptake, significantly improving mitochondrial energy production and function. Importantly, the improved functional characteristics of the mitochondria are maintained even after isolation from cells. Primed mitochondria, i.e., those enhanced by NIR‐mediated NADH uptake (P‐MT), are encapsulated in fusogenic liposomes and delivered into muscle cells with mitochondrial dysfunction. Compared to conventional mitochondria, P‐MT mitochondria promote greater mitochondrial recovery and muscle regeneration. These findings suggest that NIR‐mediated NADH delivery is an effective strategy for improving mitochondrial function, and has the potential to lead to novel treatments for mitochondrial disorders and muscle degeneration.
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issn 2198-3844
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spelling doaj-art-445c2e92977d46d5af7ec510274a94632025-08-20T03:41:59ZengWileyAdvanced Science2198-38442025-03-011212n/an/a10.1002/advs.202415303Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction ModelHui Bang Cho0Hye‐Ryoung Kim1Sujeong Lee2Chae Won Cho3Ji‐In Park4Seulki Youn5Gyuwon So6Sumin Kang7Hye Jin Kim8Keun‐Hong Park9Department of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaDepartment of Nano‐regenerative Medical Engineering College of Life Science CHA University 6F, CHA Biocomplex, Sampyeong‐Dong, Bundang‐gu Seongnam‐si 13488 Republic of KoreaAbstract Mitochondrial transfer emerges as a promising therapy for the restoration of mitochondrial function in damaged cells, mainly due to its limited immunogenicity. However, isolated mitochondria rapidly lose function because they produce little energy outside cells. Therefore, this study investigates whether near infrared (NIR)‐mediated nicotinamide adenine dinucleotide (NADH) pre‐treatment enhances mitochondrial function and stability in mitochondria‐donor cells prior to transplantation. Clinical applications of NADH, an essential electron donor in the oxidative phosphorylation process, are restricted due to the limited cellular uptake of NADH. To address this, a photo‐mediated method optimizes direct NADH delivery into cells and increases NADH absorption. L6 cells treated with NADH and irradiated with NIR enhanced NADH uptake, significantly improving mitochondrial energy production and function. Importantly, the improved functional characteristics of the mitochondria are maintained even after isolation from cells. Primed mitochondria, i.e., those enhanced by NIR‐mediated NADH uptake (P‐MT), are encapsulated in fusogenic liposomes and delivered into muscle cells with mitochondrial dysfunction. Compared to conventional mitochondria, P‐MT mitochondria promote greater mitochondrial recovery and muscle regeneration. These findings suggest that NIR‐mediated NADH delivery is an effective strategy for improving mitochondrial function, and has the potential to lead to novel treatments for mitochondrial disorders and muscle degeneration.https://doi.org/10.1002/advs.202415303mitotherapymitochondrial primingmuscle regenerationNADH deliverynear‐infrared (NIR)
spellingShingle Hui Bang Cho
Hye‐Ryoung Kim
Sujeong Lee
Chae Won Cho
Ji‐In Park
Seulki Youn
Gyuwon So
Sumin Kang
Hye Jin Kim
Keun‐Hong Park
Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
Advanced Science
mitotherapy
mitochondrial priming
muscle regeneration
NADH delivery
near‐infrared (NIR)
title Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
title_full Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
title_fullStr Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
title_full_unstemmed Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
title_short Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
title_sort near infrared mediated intracellular nadh delivery strengthens mitochondrial function and stability in muscle dysfunction model
topic mitotherapy
mitochondrial priming
muscle regeneration
NADH delivery
near‐infrared (NIR)
url https://doi.org/10.1002/advs.202415303
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