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Updated: Jun 21, 2026
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Biomimetic macrophage membrane-coated nanoparticles for targeted cardioprotection against myocardial
Hengheng Li1, Yanlin Yu2, Daiwen Yin3
1Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Abstract:
Myocardial ischaemia-reperfusion injury (MIRI) exacerbates cardiomyocyte damage through oxidative stress, inflammation, and apoptosis, limiting the efficacy of reperfusion therapies. We developed PB1-Lip@M-CST, a biomimetic nanoparticle comprising procyanidin B1 (PB1)-loaded liposomes coated with macrophage cell membranes and surface-functionalized with the cardiac-specific targeting peptide CSTSMLKAC (CST). The nanoparticles were characterized for hydrodynamic size, zeta potential, core-shell morphology, retention of macrophage surface proteins (CCR2, CD11b, CD36), high encapsulation efficiency, and sustained drug release. In vitro, PB1-Lip@M-CST markedly reduced phagocytic uptake by RAW 264.7 macrophages, enhanced internalization in HL-1 cardiomyocytes in a CST-dependent manner, and provided superior protection in CoCl2-induced hypoxia-reoxygenation models by suppressing reactive oxygen species, lipid peroxidation, proinflammatory cytokines, and apoptosis. Mechanistic studies using CXCR4-overexpressing HL-1 cells and Plerixafor-treated cells confirmed that these effects were mediated via modulation of the CXCR4-associated PI3K/AKT1 signaling pathway and restoration of the BAX/BCL-2 balance. In a mouse model of MIRI, intravenous administration of PB1-Lip@M-CST prolonged systemic circulation, with markedly enhanced cardiac accumulation (highest heart AUC) and improved therapeutic index, reduced infarct size to 25.58 ± 2.96% (versus 49.22 ± 3.03% in the model group), preserved left ventricular ejection fraction at 50.42 ± 8.74%, attenuated serum injury biomarkers, and inhibited long-term fibrosis and apoptosis, with an excellent biosafety profile. These findings establish PB1-Lip@M-CST as a novel biomimetic platform that integrates macrophage membrane-mediated immune evasion with CST-directed cardiac homing to achieve cardiac-targeted delivery of PB1 and subsequent CXCR4-dependent modulation of the PI3K/AKT1 pathway in MIRI.
Insights
A novel biomimetic nanoparticle, PB1-Lip@M-CST, effectively targets cardiac cells to reduce damage from myocardial ischemia-reperfusion injury (MIRI). This nanoparticle improves therapeutic outcomes by suppressing inflammation and apoptosis, offering a promising new treatment strategy.
Area of Science:
- Biomaterials Science and Nanotechnology
- Cardiovascular Research
- Pharmacology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) causes significant cardiomyocyte damage via oxidative stress, inflammation, and apoptosis, limiting current reperfusion therapy effectiveness.
- Developing targeted delivery systems is crucial to overcome the limitations of treating MIRI and improve therapeutic efficacy.
Purpose of the Study:
- To develop and evaluate PB1-Lip@M-CST, a novel biomimetic nanoparticle for targeted delivery of procyanidin B1 (PB1) to cardiac tissue during MIRI.
- To investigate the in vitro and in vivo efficacy of PB1-Lip@M-CST in mitigating MIRI-induced damage and explore its underlying therapeutic mechanisms.
Main Methods:
- PB1-Lip@M-CST nanoparticles were engineered using liposomes loaded with PB1, coated with macrophage cell membranes, and functionalized with a cardiac-specific peptide (CSTSMLKAC).
- Characterization included size, zeta potential, morphology, surface protein retention, encapsulation efficiency, and drug release kinetics.
- In vitro studies assessed cellular uptake and protection against hypoxia-reoxygenation injury in cardiomyocytes, while in vivo studies utilized a mouse MIRI model to evaluate cardiac accumulation, infarct size, cardiac function, and long-term effects.
Main Results:
- PB1-Lip@M-CST demonstrated reduced macrophage uptake, enhanced cardiomyocyte internalization, and significant protection against oxidative stress, inflammation, and apoptosis in vitro.
- In vivo, nanoparticles showed prolonged circulation, enhanced cardiac accumulation, reduced infarct size (25.58% vs. 49.22%), preserved ejection fraction (50.42%), and inhibited long-term fibrosis and apoptosis.
- Therapeutic effects were linked to CXCR4-dependent modulation of the PI3K/AKT1 pathway and BAX/BCL-2 balance.
Conclusions:
- PB1-Lip@M-CST represents a novel biomimetic platform combining immune evasion and cardiac-specific targeting for effective PB1 delivery in MIRI.
- The platform successfully mitigates MIRI by modulating key signaling pathways and exhibits a favorable biosafety profile, suggesting its potential as an advanced therapeutic strategy for cardiovascular diseases.
