Nanoparticles with reprogramming of mitochondrial respiratory chain complex and epigenetic modifications functions
Yiping Liu1, Liangjing Xin1, Si Wang1
1Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, PR China.
Abstract:
Current therapies primarily focusing on osteoporosis often fail to address the root relationship between metabolic reprogramming and epigenetic modification alterations. Developing an efficient therapeutic approach with dual-pronged functionality for the treatment of osteoporosis represents a noteworthy challenge. Herein, samples from humans and rats with osteoporosis presented in this study underscore the correlation between mitochondrial metabolism, epigenetic modifications, and osteoporotic bone loss. Inspired by this, we focus on designing a nano-therapy that serves as a strategy, targeting both the maintenance of metabolic homeostasis and the modulation of epigenetic modifications, thereby achieving a dual-functional effect in the treatment of osteoporosis. Accordingly, 4-octyl itaconate (OI), which exhibits immunometabolic activity and regulates epigenetic modifications, was encapsulated within mesoporous silica (MSN) and further modified with a cerium ion-coordinated tannic acid (Ce-TA) supramolecular network on its surface for boosting antioxidant properties. In brief, MSN-OI@Ce-TA (MOCT NPs) exhibit synergistically enhanced antioxidant capabilities in pro-inflammatory macrophages and alleviates osteoporotic bone loss by restoring mitochondrial respiratory chain complex function, remodeling DNA and histone modifications, and thereby restoring osteoimmune homeostasis. Overall, these findings highlight the compelling dual treatment mechanisms of MOCT NPs, providing a theoretical basis for the management of osteoporosis.
Insights
This study introduces a novel nano-therapy (MSN-OI@Ce-TA NPs) that simultaneously targets metabolic and epigenetic changes to treat osteoporosis. The dual-action approach effectively combats bone loss and restores immune balance.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Osteoporosis Research
Background:
- Current osteoporosis therapies often overlook the interplay between metabolic reprogramming and epigenetic alterations.
- Osteoporotic bone loss is linked to mitochondrial dysfunction and epigenetic modifications.
Purpose of the Study:
- To develop a dual-functional nano-therapy targeting metabolic homeostasis and epigenetic modifications for osteoporosis treatment.
- To investigate the therapeutic potential of MSN-OI@Ce-TA NPs in an osteoporosis model.
Main Methods:
- Encapsulation of 4-octyl itaconate (OI) in mesoporous silica nanoparticles (MSN).
- Surface modification with a cerium ion-coordinated tannic acid (Ce-TA) supramolecular network.
- Evaluation of antioxidant properties and therapeutic effects on osteoporotic bone loss in vitro and in vivo.
Main Results:
- MSN-OI@Ce-TA NPs (MOCT NPs) demonstrated synergistic antioxidant effects in macrophages.
- MOCT NPs restored mitochondrial respiratory chain complex function and remodeled DNA/histone modifications.
- Treatment alleviated osteoporotic bone loss and restored osteoimmune homeostasis.
Conclusions:
- MOCT NPs offer a promising dual-treatment strategy for osteoporosis by addressing both metabolic and epigenetic dysregulation.
- This nano-therapy provides a novel theoretical basis for managing osteoporosis through combined immunometabolic and epigenetic modulation.
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