A multifunctional biomimetic nanoplatform targeting mitochondrial dynamics and oxidative stress for heart failure therapy.
8 affiliations
- 1Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
- 2Department of Cardiology, Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China.
- 3Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
- 4School of Medicine, Tongji University, Shanghai, 200092, China.
- 5Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
- 6Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. [email protected].
- 7Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. [email protected].
- 8Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. [email protected].
Abstract
Background: Heart failure (HF) presents a significant global health challenge, caused by mitochondrial dysfunction, oxidative stress, and chronic inflammation, all of which impair cardiac function. This investigation introduces a new nanoplatform, PCM-refined M2 macrophage membrane-coated CeO2 nanozyme loaded with PGAM5 siRNA (P-MM@Ps-CeO2), that can target these interconnected disease pathways.
Results: Mechanistically, silencing PGAM5 with this nanoplatform precludes the dephosphorylation of Drp1 at Ser637, thereby lessening excessive mitochondrial fission. Yet, it restores the DDX17- BCL6 control mechanism to decrease Drp1 levels, ultimately maintaining mitochondrial balance. CeO2 nanozymes break down reactive oxygen species (ROS), Attenuating cellular oxidative imbalance, while M2 macrophage membranes improve anti-inflammatory targeting to inflamed heart tissue, with PCM ensuring delivery precisely to the heart. In vitro, P-MM@Ps-CeO2 re-established baseline 90% of the viability in lipopolysaccharide- worsened HL-1 cardiomyocytes, attenuated ROS by 70%, and lowered Pro-inflammatory cytokines (IL-1β, TNF-α) by up to 67%. It also preserved mitochondrial integrity, increased ATP production, and lowered apoptosis by 70%. In vivo, in a doxorubicin-induced HF mouse model, the nanoplatform improved ejection fraction to 65% and fractional shortening to 35%, reduced myocardial fibrosis by 30% and apoptosis by 70%, and increased cardiac accumulation by 2.5 times.
Conclusions: These outcomes indicate that P-MM@Ps-CeO₂ transcends conventional HF interventions, which typically fail to address mitochondrial abnormalities. The nanoplatform showed excellent biocompatibility, with minimal hemolytic activity and no detectable organ toxicity, supporting its potential for clinical use. By simultaneously targeting mitochondrial turnover, reactive oxygen species (ROS) stress, and inflammation, P-MM@Ps-CeO2 yields an advantageous pioneering treatment modality, HF, highly capable of improving analysis outcomes for the worldwide HF cohort.
Graphical abstract: Schematic illustrating the in-situ co-precipitation of PGAM5 siRNA during CeO₂ nanozyme formation (Step 1), followed by M2 macrophage membrane coating and PCM-mediated cardiac targeting (Step 2). Schematic illustration of the therapeutic mechanism by which engineered nanozymes (P MM@Ps CeO₂) ameliorate heart failure through regulation of mitochondrial dynamics and inhibition of cardiomyocyte apoptosis
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04839-8.
Related
- Biomimetic sequential targeted nanoplatform for synergistic thrombolysis in ischemic stroke.
- Copper‐Doped Prussian Blue Nanozymes With Hyaluronic Acid‐Mediated Targeting Alleviate Oxidative Stress and Regulate Cholesterol Handling for Atherosclerosis Therapy
- Disruption of Mitochondrial Bioenergetics Links Oxidative Stress-Mediated Apoptosis to Hepatorenal Injury Following Sub-Chronic Exposure to Titanium Dioxide Nanoparticles.
- From Mitochondrial Targeting to Microbial Killing: Twinkle-Derived Peptides as an Emerging Class of Potent AMPs
- Cobalt oxide nanoparticles disrupt cellular homeostasis through oxidative genomic instability and mitochondrial stress, driving necrosis in non-small lung cancer cells
BibTeX
@article{fang2026multifunctional,
title = {{A multifunctional biomimetic nanoplatform targeting mitochondrial dynamics and oxidative stress for heart failure therapy.}},
author = {Ming Fang and Alimujiang Maimaitijiang and Limin Fan and Yixin Liu and Wei Wang and Xiangdong Meng and Jingyi Cao and Lin Shen and Bing Deng and Wang Zheng and Fanglin Lu and Yu Zhuang},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04839-8},
url = {https://europepmc.org/article/MED/42968159},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A multifunctional biomimetic nanoplatform targeting mitochondrial dynamics and oxidative stress for heart failure therapy.
AU - Ming Fang
AU - Alimujiang Maimaitijiang
AU - Limin Fan
AU - Yixin Liu
AU - Wei Wang
AU - Xiangdong Meng
AU - Jingyi Cao
AU - Lin Shen
AU - Bing Deng
AU - Wang Zheng
AU - Fanglin Lu
AU - Yu Zhuang
PY - 2026
DA - 2026/07/25
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04839-8
UR - https://europepmc.org/article/MED/42968159
AB - Background: Heart failure (HF) presents a significant global health challenge, caused by mitochondrial dysfunction, oxidative stress, and chronic inflammation, all of which impair cardiac function. This investigation introduces a new nanoplatform, PCM-refined M2 macrophage membrane-coated CeO2 nanozyme loaded with PGAM5 siRNA (P-MM@Ps-CeO2), that can target these interconnected disease pathways. Results: Mechanistically, silencing PGAM5 with this nanoplatform precludes the dephosphorylation of Drp1 at Ser637, thereby lessening excessive mitochondrial fission. Yet, it restores the DDX17- BCL6 control mechanism to decrease Drp1 levels, ultimately maintaining mitochondrial balance. CeO2 nanozymes break down reactive oxygen species (ROS), Attenuating cellular oxidative imbalance, while M2 macrophage membranes improve anti-inflammatory targeting to inflamed heart tissue, with PCM ensuring delivery precisely to the heart. In vitro, P-MM@Ps-CeO2 re-established baseline 90% of the viability in lipopolysaccharide- worsened HL-1 cardiomyocytes, attenuated ROS by 70%, and lowered Pro-inflammatory cytokines (IL-1β, TNF-α) by up to 67%. It also preserved mitochondrial integrity, increased ATP production, and lowered apoptosis by 70%. In vivo, in a doxorubicin-induced HF mouse model, the nanoplatform improved ejection fraction to 65% and fractional shortening to 35%, reduced myocardial fibrosis by 30% and apoptosis by 70%, and increased cardiac accumulation by 2.5 times. Conclusions: These outcomes indicate that P-MM@Ps-CeO₂ transcends conventional HF interventions, which typically fail to address mitochondrial abnormalities. The nanoplatform showed excellent biocompatibility, with minimal hemolytic activity and no detectable organ toxicity, supporting its potential for clinical use. By simultaneously targeting mitochondrial turnover, reactive oxygen species (ROS) stress, and inflammation, P-MM@Ps-CeO2 yields an advantageous pioneering treatment modality, HF, highly capable of improving analysis outcomes for the worldwide HF cohort. Graphical abstract: Schematic illustrating the in-situ co-precipitation of PGAM5 siRNA during CeO₂ nanozyme formation (Step 1), followed by M2 macrophage membrane coating and PCM-mediated cardiac targeting (Step 2). Schematic illustration of the therapeutic mechanism by which engineered nanozymes (P MM@Ps CeO₂) ameliorate heart failure through regulation of mitochondrial dynamics and inhibition of cardiomyocyte apoptosis Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04839-8.
SN - 1477-3155
ER -