Liposomes for drug delivery to mitochondria.

Efficacy of therapeutically active drugs known to act on intracellular targets can be enhanced by specific delivery to the site of action. Triphenylphosphonium cations can be used to create subcellular targeted liposomes that efficiently deliver drugs to mitochondria, thus enhancing their therapeutic action.

Nanocarrier-assisted sub-cellular targeting to the site of mitochondria improves the pro-apoptotic activity of paclitaxel.

Many drug molecules exert their biological action on intracellular molecular targets present on or inside various cellular organelles. Consequently, it has become more evident that the efficiency and efficacy of drug action is dependent largely on how well an unaided drug molecule is able to reach its intracellular target. We hypothesized that the biological action of such drug molecules might be improved by specific delivery to the appropriate sub-cellular site by a pharmaceutical carrier designed for the purpose.

Organelle-targeted nanocarriers: specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo.

To further increase the therapeutic activity of drugs known to act on intracellular target sites, in vivo drug delivery approaches must actively mediate the specific delivery of drug molecules to the subcellular site of action. We show here that surface modification of nanocarriers with mitochondriotropic triphenylphosphonium cations facilitates the efficient subcellular delivery of a model drug to mitochondria of mammalian cells and improves its activity in vitro and in vivo.

Xenogenic transfer of isolated murine mitochondria into human rho0 cells can improve respiratory function.

Mitochondrial DNA mutations are the direct cause of several physiological disorders and are also associated with the aging process. The modest progress made over the past two decades towards manipulating the mitochondrial genome and understanding its function within living mammalian cells means that cures for mitochondrial DNA mutations are still elusive. Here, we report that transformed mammalian cells internalize exogenous isolated mitochondria upon simple co-incubation.

Mitochondria-specific nanotechnology.

Mitochondrial research has made an enormous leap since mitochondrial DNA mutations were identified as a primary cause for human diseases in 1988 and the organelle's crucial role in apoptosis was identified during the 1990s. Considerable progress has been made in identifying the molecular components of the mitochondrial machinery responsible for life and cell death; however, effective therapies for diseases caused by mitochondrial dysfunction remain elusive. An impediment to manipulating, probing and assessing the functional components of mammalian mitochondria within living cells is their limited accessibility to direct physical, biochemical and pharmacological manipulation.

Gene therapy of the other genome: the challenges of treating mitochondrial DNA defects.

Human mitochondrial DNA is a 16.5 kb circular DNA molecule located inside the mitochondrial matrix. Although accounting for only about 1% of total cellular DNA, defects in mitochondrial DNA have been found to have major effects on human health.

Liposomes and liposome-like vesicles for drug and DNA delivery to mitochondria.

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.

Mitochondriotropic liposomes.

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. Increasing pharmacological efforts toward therapeutic interventions have been made leading to the emergence of "Mitochondrial Medicine" as a 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.

Mitochondrial leader sequence--plasmid DNA conjugates delivered into mammalian cells by DQAsomes co-localize with mitochondria.

In the last decade the increase in therapeutic strategies aimed at mitochondrial targets has resulted in the need for novel delivery systems for the selective delivery of drugs and DNA into mitochondria. In this study, we have continued our efforts towards the development of the first mitochondriotropic drug and DNA delivery system (DQAsomes). Prepared from derivatives of the self-assembling mitochondriotropic bola-amphiphile dequalinium chloride, these vesicles bind and transport DNA to mitochondria in living mammalian cells where upon they have been shown to release the DNA on contact with mitochondrial membranes.