Development of Multi-layered nano-device for mitochondrial drug delivery and an innovative approach for mitochondrial disease' therapy

线粒体功能障碍与多种人类疾病有关。线粒体疾病的有效医疗疗法最终将需要一个最佳的药物输送系统，这很可能通过细胞内转运的纳米技术的创新来实现。为了实现有效的线粒体药物传递，需要两个独立的过程，即“细胞质通过细胞膜传递”和“线粒体通过线粒体膜传递”。在这里，我们报道了一种双功能Mito-Porter(DF-Mito-Porter)的开发，它是一种集高效细胞质递送和线粒体大分子递送于一体的纳米载体。我们表明，DF-Mito-Porter有效地将外源性大分子生物分子输送到线粒体基质中，并展示了其在针对线粒体DNA的治疗中的潜在用途。

Mitochondrial dysfunction is associated with a variety of human diseases. Effective medical therapies for mitochondrial diseases will ultimately require an optimal drug delivery system, which will likely be achieved through innovations in the nanotechnology of intracellular trafficking. To achieve efficient mitochondrial drug delivery, two independent processes, i.e., "cytoplasmic delivery through the cell membrane" and "mitochondrial delivery through the mitochondrial membrane" are required. Here, we report the development of a Dual Function MITO-Porter (DF-MITO-Porter), a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery. We show that the DF-MITO-Porter effectively delivers exogenous macro-biomolecules into the mitochondrial matrix, and provide a demonstration of its potential use in therapies aimed at mitochondrial DNA.