Weissig Volkmar, Boddapati Sarathi V, Cheng Shing-Ming, D'Souza Gerard G M
Northeastern University, Bouve College of Health Sciences, School of Pharmacy, Department of Pharmaceutics, Boston, MA 02115, USA.
J Liposome Res. 2006;16(3):249-64. doi: 10.1080/08982100600851169.
Mitochondrial research is presently one of the fastest growing disciplines in biomedicine. Since the early 1990s, it has become increasingly evident that mitochondrial dysfunction contributes to a large variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Most remarkably, mitochondria, the "power house" of the cell, have also become accepted as the "motor of cell death" reflecting their recognized key role during apoptosis. Based on these recent exciting developments in mitochondrial research, increasing pharmacological efforts have been made leading to the emergence of "Mitochondrial Medicine" as a whole new field of biomedical research. The identification of molecular mitochondrial drug targets in combination with the development of methods for selectively delivering biologically active molecules to the site of mitochondria will eventually launch a multitude of new therapies for the treatment of mitochondria-related diseases, which are based either on the selective protection, repair, or eradication of cells. Yet, while tremendous efforts are being undertaken to identify new mitochondrial drugs and drug targets, the development of mitochondria-specific drug carrier systems is lagging behind. To ensure a high efficiency of current and future mitochondrial therapeutics, colloidal vectors, i.e., delivery systems, need to be developed able to selectively transport biologically active molecules to and into mitochondria within living human cells. Here we review ongoing efforts in our laboratory directed toward the development of different phospholipid- and non-phospholipid-based mitochondriotropic drug carrier systems.
线粒体研究目前是生物医学领域中发展最快的学科之一。自20世纪90年代初以来，越来越明显的是，线粒体功能障碍与多种人类疾病有关，从神经退行性疾病、神经肌肉疾病、肥胖症、糖尿病到缺血再灌注损伤和癌症。最引人注目的是，线粒体作为细胞的“动力源”，也被公认为“细胞死亡的驱动者”，这反映了它们在细胞凋亡过程中公认的关键作用。基于线粒体研究的这些最新令人兴奋的进展，人们在药理学方面做出了越来越多的努力，导致“线粒体医学”作为生物医学研究的一个全新领域应运而生。线粒体分子药物靶点的鉴定，以及将生物活性分子选择性地递送至线粒体部位的方法的开发，最终将催生众多治疗线粒体相关疾病的新疗法，这些疗法要么基于对细胞的选择性保护、修复，要么基于对细胞的根除。然而，尽管人们正在付出巨大努力来鉴定新的线粒体药物和药物靶点，但线粒体特异性药物载体系统的开发却滞后了。为了确保当前和未来线粒体治疗的高效性，需要开发能够将生物活性分子选择性地运输到活的人类细胞内线粒体并进入线粒体的胶体载体，即递送系统。在此，我们综述了我们实验室为开发不同的基于磷脂和非磷脂的线粒体靶向药物载体系统所做的持续努力。
