Mitochondria-Targeting Particles

Abstract

Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity. To reach mitochondria, therapeutic molecules need to not only gain access to specific organs, but also to overcome multiple barriers such as the cell membrane and the outer and inner mitochondrial membranes. Cellular and mitochondrial barriers can be potentially overcome through the design of mitochondriotropic particulate carriers capable of transporting drug molecules selectively to mitochondria. These particulate carriers or vectors can be made from lipids (liposomes), biodegradable polymers, or metals, protecting the drug cargo from rapid elimination and degradation in vivo. Many formulations can be tailored to target mitochondria by the incorporation of mitochondriotropic agents onto the surface and can be manufactured to desired sizes and molecular charge. Here, we summarize recently reported strategies for delivering therapeutic molecules to mitochondria using various particle-based formulations.

Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury

“…There are various TPP-conjugated drug molecules and bioactive compounds such as, vitamin E (MitoVit E) 17 , a ubiquinone derivative (MitoQ) 18 and doxorubicin 19 . There are also liposomes formulated with TPP in the lipid layers to target mitochondria 20 . TPP can be conjugated to PLGA-block-poly(ethylene glycol) (PEG) polymer and blended with either non-targeted PLGA-block-PEG-OH or PLGA-COOH to prepare solid PLGA particles using a nanoprecipitation method 21 .…”

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

“…Another challenge for targeted drug delivery to the mitochondria is endocytosis. To escape from the endosome, the carriers must be designed to contain ligands facilitating such transport 92 …”

The Potential for Nanotechnology to Improve Delivery of Therapy to the Acute Ischemic Heart

“…[5,33] Calcium overload has a negative effect on the contractility of the myocardium, and mPTP formation is linked to cell death by necrotic and apoptotic mechanisms. [34] Also, there are well-established connections between intracellular calcium and ROS concentrations, and subsequent myocardial dysfunction, hypertrophy, and remodeling. [2] Calcium mishandling and overproduction of ROS can activate Ca 2+ -calmodulin-dependent protein kinase II (CaMKII), which contributes to arrhythmogenesis through ryanodine receptor stimulation (RyR) and increased sarcoplasmic reticulum Ca 2+ leak, triggering spontaneous action potentials.…”