Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia‒reperfusion injury in heart transplantation.

Yuan S, Che Y, Wang Z, Xing K, Xie X, Chen Y

Journal of translational medicine20 Dec 2023Cited by 21 (Europe PMC)

PMID38124174PMCIDPMC10734076DOI10.1186/s12967-023-04763-7PepBankPUB-38124174

Summary

BackgroundHeart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model.MethodsHybrid nanoparticles composed of CaCO₃/CaP/biotinylated-carboxymethylchitosan (CaCO₃/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation.ResultsCoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation.ConclusionsCoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In a mouse heart transplantation model, CoQ10-loaded SS31-targeted nanoparticles improved cardiac graft function.
In plain wordsIn mice, nanoparticles that carry CoQ10 and an SS31 targeting peptide improved the function of transplanted hearts. SS31 alone was not tested.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCardiac graft function after cold ischaemia
Study
mousen: not reported in source
murine heterotopic cardiac transplantation
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation.
1 context sentence(design, population, supporting numbers)
Summary · context
Hybrid nanoparticles composed of CaCO₃/CaP/biotinylated-carboxymethylchitosan (CaCO₃/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3812417402
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In a mouse heart transplantation model, CoQ10-loaded SS31-targeted nanoparticles attenuated mitochondrial oxidative injury and inflammation in the graft.
In plain wordsIn mice, nanoparticles that carry CoQ10 and an SS31 targeting peptide reduced oxidative injury and inflammation in transplanted hearts. SS31 alone was not tested.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial oxidative injury and inflammation in graft
Study
mousen: not reported in source
murine heterotopic cardiac transplantation
Outcome group
Inflammation markers · Cardiovascular
Source sentences
Summary
attenuating mitochondrial oxidative injury and inflammation.
1 context sentence(design, population, supporting numbers)
Summary · context
Hybrid nanoparticles composed of CaCO₃/CaP/biotinylated-carboxymethylchitosan (CaCO₃/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3812417403
03LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In H9c2 cells under hypoxia-reoxygenation, CoQ10-loaded SS31-targeted nanoparticles ameliorated oxidative stress damage and mitochondrial injury.
In plain wordsIn cells, nanoparticles that carry CoQ10 and an SS31 targeting peptide reduced oxidative damage and mitochondrial injury. SS31 alone was not tested.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseOxidative stress damage and mitochondrial injury in cold I/R
Study
n: not reported in source
H9c2 cells, hypoxia-reoxygenation model
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury.
1 context sentence(design, population, supporting numbers)
Summary · context
Hybrid nanoparticles composed of CaCO₃/CaP/biotinylated-carboxymethylchitosan (CaCO₃/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3812417401

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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