Targeting drugs to mitochondria

Pharmacokinetics on a microscale: visualizing Cy5-labeled oligonucleotide release from poly(n-butylcyanoacrylate) nanocapsules in cells

“…23 Further, they have a high membrane potential of 180-200 mV and contain their own genome. 20 Rhee et al demonstrated that the mitochondrial membrane potential was indeed responsible for accumulation of the cyanine-labeled oligonucleotides used in their work. 13 Using carbonyl cyanide m-chlorophenyl hydrazone (CCCP) as an uncoupler, the mitochondrial membrane potential was reduced, resulting in decreased fluorescence intensity of colocalized cyanine dye-labeled oligonucleotides and appearance of diffuse fluorescence.…”

“…Mitochondrial targeting is of growing interest in the research setting at present. 20 Mitochondria are the main producers of adenosine triphosphate in eukaryotic cells, and are also involved in other metabolic pathways, like oxidation of fatty acids, gluconeogenesis, and the citrate cycle. 21 They also have a key role in the apoptosis mechanism, which can be exploited in cancer chemotherapy.…”

Poisoning of Mitochondrial Topoisomerase I by Lamellarin D

“…Moreover, recent evidence revealed that mtDNA amounts regulate response to chemotherapy (Singh et al, 1999;Naito et al, 2008;Hsu et al, 2010). Different strategies have been reported for targeting drugs to mitochondria (Heller et al, 2012;Yousif et al, 2009), including nanoparticles (Marrache and Dhar, 2012). Recently, the two most used anticancer agents, cisplatin (Wisnovsky et al, 2013) and doxorubicin (Chamberlain et al, 2013), have been targeted to mitochondrial DNA.…”

Mitochondrial disorders: aetiologies, models systems, and candidate therapies

“…Development of potent methods for DNA delivery to mitochondria will find broad utility in the future generation of transgenic animals and in exploring novel therapies for mitochondrial disorders. Delivering molecules to mitochondria Although an array of methods has been explored to achieve delivery of nucleotides and peptides to mitochondria [58][59][60][61], few data exist on the relative efficiencies of methodologies, levels of delivery to cytoplasm versus subcellular targets, proportions of mitochondria targeted, and longevity of delivered molecules. Nevertheless, delivery technologies under development are detailed below and provide an overview of the various approaches being considered.…”