Functionalized nanoparticles provide early cardioprotection after acute myocardial infarction
Functionalized nanoparticles provide early cardioprotection after acute myocardial infarction
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DOI：
10.1016/j.jconrel.2013.04.022
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发表时间：
2013-09-10
影响因子：
10.8
通讯作者：
Hsieh, Patrick C. H.
中科院分区：
文献类型：
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作者：
Chang, Ming-Yao;Yang, Yu-Jen;Hsieh, Patrick C. H.
纳米技术的最新发展为诊断和癌症治疗创造了相当大的潜力。相比之下，纳米技术在组织修复或再生中的应用在很大程度上尚未探索。我们假设，心肌内注射胰岛素样生长因子（IGF）-1-复合聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米颗粒（PLGA-IGF-1 NPs）增加IGF-1的保留，诱导Akt磷酸化，并提供急性心肌梗死（MI）后的早期心脏保护。我们合成了3种不同尺寸的PLGA颗粒（60 nm，200 nm和1 μ m），使用静电力将其与IGF-1复合以保持IGF-1的生物学功能。然后，我们直接在MI后的心脏中注射PLGA-IGF-1 NPs。与其他两种较大的颗粒相比，60 nm大小的PLGA-IGF-1 NPs携带更多的IGF-1，并在培养的心肌细胞中诱导更多的Akt磷酸化。PLGA-IGF-1纳米粒也延长Akt激活心肌细胞达24小时，并以剂量依赖性方式防止阿霉素诱导的心肌细胞凋亡。在体内，PLGA-IGF-1 NP处理在2、6、8和24 h时在心肌中比单独IGF-1处理显著保留更多的IGF-1。仅在接受PLGA-IGF-1 NP处理的心脏中，在MI后24小时的心肌细胞中检测到Akt磷酸化，但在接受PBS、IGF-1或PLGA NP注射的心脏中未检测到Akt磷酸化。重要的是，在小鼠实验性MI后21天，单次心肌内注射PLGA-IGF-1 NPs足以防止心肌细胞凋亡（P < 0.001），减少梗死面积（P < 0.05），并改善左心室射血分数（P < 0.01）。我们的研究结果不仅证明了基于纳米颗粒的技术作为治疗MI的新方法的潜力，而且对将该技术转化为缺血性心血管疾病的临床治疗具有重要意义。(C)2013年爱思唯尔B。V.保留所有权利。
Recent developments in nanotechnology have created considerable potential toward diagnosis and cancer therapy. In contrast, the use of nanotechnology in tissue repair or regeneration remains largely unexplored. We hypothesized that intramyocardial injection of insulin-like growth factor (IGF)-1-complexed poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-IGF-1 NPs) increases IGF-1 retention, induces Akt phosphorylation, and provides early cardioprotection after acute myocardial infarction (MI). We synthesized 3 different sizes of PLGA particles (60 nm, 200 nm, and 1 mu m) which were complexed with IGF-1 using electrostatic force to preserve the biological function of IGF-1. Afterward, we injected PLGA-IGF-1 NPs in the heart after MI directly. Compared with the other two larger particles, the 60 nm-sized PLGA-IGF-1 NPs carried more IGF-1 and induced more Akt phosphorylation in cultured cardiomyocytes. PLGA-IGF-1 NPs also prolonged Akt activation in cardiomyocytes up to 24 h and prevented cardiomyocyte apoptosis induced by doxorubicin in a dose-dependent manner. In vivo, PLGA-IGF-1 NP treatment significantly retained more IGF-1 in the myocardium than the IGF-1 alone treatment at 2, 6, 8, and 24 h. Akt phosphorylation was detected in cardiomyocytes 24 h post-MI only in hearts receiving PLGA-IGF-1 NP treatment, but not in hearts receiving injection of PBS, IGF-1 or PLGA NPs. Importantly, a single intramyocardial injection of PLGA-IGF-1 NPs was sufficient to prevent cardiomyocyte apoptosis (P < 0.001), reduce infarct size (P < 0.05), and improve left ventricle ejection fraction (P < 0.01) 21 days after experimental MI in mice. Our results not only demonstrate the potential of nanoparticle-based technology as a new approach to treating MI, but also have significant implications for translation of this technology into clinical therapy for ischemic cardiovascular diseases. (C) 2013 Elsevier B. V. All rights reserved.