Mitochondrial Targeting Probes, Drug Conjugates, and Gene Therapeutics

Unlocking mitochondrial drug targets: The importance of mitochondrial transport proteins

“…A widely used approach in drug delivery is to significantly increase the drug concentration in target cells or organelles versus other compartments, to increase therapeutic efficacy and minimize side effects. In mitochondrial targeting, however, one of the inherent difficulties is the largely impermeable mitochondrial (inner) membrane 156,233 . So far, a variety of different approaches has been developed.…”

“…Transport of a variety of biologically active molecules, cargos and drugs can be mediated by these MPPs. 233,[241][242][243] These kind of peptides have been used for mitochondrial targeting of cytostatics such as cisplatin and doxorubicin. 155,239,240,[244][245][246] Recently, peptide-based mitochondrial gene targeting using antisense oligonucleotides showed to be promising in affecting the function of mitochondria.…”

“…Typical features of these peptides are the short, positively charged sequences varying from 4 to 40 amino acids in length, capable of crossing plasma or organellar membranes resulting in internalization into cells and ultimately mitochondria as target of interest. Transport of a variety of biologically active molecules, cargos and drugs can be mediated by these MPPs 233,241–243 . These kind of peptides have been used for mitochondrial targeting of cytostatics such as cisplatin and doxorubicin 155,239,240,244–246 .…”

“…In mitochondrial targeting, however, one of the inherent difficulties is the largely impermeable mitochondrial (inner) membrane. 156,233 So far, a variety of different approaches has been developed. According to the Nernst equation, the internal negative membrane potential drives the uptake of lipophilic cations into the matrix, which increases 10-fold for every 61.5 mV difference, leading to a 200-400 fold higher accumulation of lipophilic cations.…”