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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Microenvironment-Responsive Nanomedicine Enables Vertical Modulation of Mitochondrial Pathological Networks in
Jue Wang1,2, Jia Zhou1,3,4, Wenqin Yuan2
1Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Myocardial ischemia-reperfusion injury (MIRI) is a severe and largely unavoidable complication of reperfusion therapy and remains a major determinant of poor outcomes after acute myocardial infarction. Here, we developed a mitochondria-targeted, ischemic microenvironment-responsive nanotherapeutic, termed Berberine/Isoliensinine-loaded Melanin Nanocomposite (BIM), by co-encapsulating the anti-inflammatory agent berberine (BBR) and the anti-apoptotic agent isoliensinine (ILS) within a melanin capsule with a controllable channel (MCC). Owing to its appropriate size, negative surface charge, and dual responsiveness to acidic pH and reactive oxygen species, BIM preferentially accumulates in injured myocardium and targets damaged mitochondria, enabling precise drug release at the pathological core. Through a structured pharmacological design, MCC scavenges mitochondrial reactive oxygen species, BBR suppresses inflammatory signaling, and ILS inhibits intrinsic apoptosis, together achieving vertical modulation of mitochondrial pathological networks. Consequently, BIM attenuates oxidative stress, limits inflammatory amplification, reduces cardiomyocyte apoptosis, and markedly decreases infarct size. These findings establish mitochondria-centered vertical network modulation as a precise therapeutic strategy for MIRI.
Insights
A novel nanotherapeutic, Berberine/Isoliensinine-loaded Melanin Nanocomposite (BIM), effectively targets mitochondria to combat myocardial ischemia-reperfusion injury (MIRI). BIM reduces oxidative stress, inflammation, and apoptosis, significantly decreasing infarct size in MIRI.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Nanomedicine
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a critical complication following acute myocardial infarction, leading to significant patient morbidity.
- Current reperfusion therapies, while necessary, can exacerbate cardiac damage through MIRI.
Purpose of the Study:
- To develop and evaluate a novel mitochondria-targeted nanotherapeutic for precise treatment of MIRI.
- To investigate the efficacy of Berberine/Isoliensinine-loaded Melanin Nanocomposite (BIM) in mitigating MIRI at the molecular and cellular levels.
Main Methods:
- Co-encapsulation of berberine (BBR) and isoliensinine (ILS) into a melanin capsule with a controllable channel (MCC) to form BIM.
- Characterization of BIM for size, surface charge, and responsiveness to acidic pH and reactive oxygen species (ROS).
- In vivo evaluation of BIM's therapeutic effects on MIRI, including infarct size reduction and molecular pathway modulation.
Main Results:
- BIM demonstrated preferential accumulation in injured myocardium and targeted damaged mitochondria due to its physicochemical properties.
- BIM effectively scavenged mitochondrial ROS, suppressed inflammatory signaling via BBR, and inhibited apoptosis via ILS.
- Significant reduction in oxidative stress, inflammation, cardiomyocyte apoptosis, and infarct size was observed in MIRI models treated with BIM.
Conclusions:
- Mitochondria-centered vertical network modulation represents a precise therapeutic strategy for MIRI.
- The developed BIM nanotherapeutic offers a promising approach to attenuate MIRI and improve outcomes after acute myocardial infarction.
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