Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Int J Mol Sci. 2021 Dec 22;23(1):112. doi: 10.3390/ijms23010112.
The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The β-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the β-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the β-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.
用于治疗心血管疾病的药物传递系统的发展是一个非常关注的领域。我们在此报告了对心肌线粒体靶向脂质体的治疗潜力的评估，这是我们实验室之前开发的一种用于靶向胰腺β细胞的多功能包膜型纳米装置（β-MEND）。白藜芦醇（RES）是一种具有心脏保护作用的天然多酚化合物，被包裹在β-MEND（β-MEND（RES））中，并使用大鼠心肌细胞（H9c2 细胞）评估其功效。β-MEND（RES）很容易被 H9c2 细胞摄取，如荧光激活细胞分选器数据所证实，并通过共聚焦激光扫描显微镜观察到与细胞内线粒体共定位。通过 Seahorse XF 分析仪评估心肌线粒体功能，结果表明β-MEND（RES）可显著激活细胞最大呼吸能力。此外，Premix WST-1 测定证实β-MEND（RES）对 H9c2 细胞没有细胞毒性。这是首次报道使用包裹 RES 的心肌线粒体靶向脂质体来激活线粒体功能，这是通过 Seahorse XF 分析仪的分析得到明确证实的。
