Abstract Cardiomyopathy caused by mitochondrial dysfunction associated with the mutation/deletion of mitochondrial DNA has been reported, and nucleic acid therapy targeting cardiac mitochondria represents a possible therapy for treating these diseases. Such a treatment, however, has not yet been achieved because delivering nucleic acids to mitochondria of cardiac muscle is difficult. In this study, H9c2 cells a type of rat cardiac myoblasts, were used as model cardiac muscle cells. The use of a lipid composition used to prepare the β-MEND (where MEND denotes multifunctional envelope-type nano device) permitted the particles to be efficiently internalized by H9c2 cells, as evidenced by flow cytometry analyses. Intracellular observations by confocal laser scanning microscopy showed that the β-MEND efficiently accumulated in mitochondria of H9c2 cells. We also constructed an RP/β-MEND that contained a mitochondrial RNA aptamer to achieve mitochondrial delivery in H9c2 cells. The successful direct mitochondrial transfection of exogenous RNA was confirmed using these carrier systems, based on PCR experiments after reverse transcription. Thus, the β-MEND holds promise as a direct mitochondrial transfection system for delivering nucleic acids targeted to H9c2 cells.

中文翻译：

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用于将核酸线粒体递送至心肌细胞的纳米载体

摘要 已报道了与线粒体 DNA 突变/缺失相关的线粒体功能障碍引起的心肌病，靶向心脏线粒体的核酸疗法代表了治疗这些疾病的可能疗法。然而，这种治疗尚未实现，因为将核酸递送到心肌的线粒体是困难的。在这项研究中，H9c2 细胞是一种大鼠心肌成肌细胞，被用作模型心肌细胞。使用用于制备 β-MEND（其中 MEND 表示多功能包膜型纳米装置）的脂质组合物允许 H9c2 细胞有效地内化颗粒，如流式细胞术分析所证明的那样。通过共聚焦激光扫描显微镜进行的细胞内观察表明，β-MEND 在 H9c2 细胞的线粒体中有效积累。我们还构建了一个包含线粒体 RNA 适配体的 RP/β-MEND，以在 H9c2 细胞中实现线粒体递送。基于逆转录后的 PCR 实验，使用这些载体系统证实了外源 RNA 的成功直接线粒体转染。因此，β-MEND 有望作为一种直接的线粒体转染系统，用于将核酸靶向 H9c2 细胞。