From Serendipity to Mitochondria-Targeted Nanocarriers

Abstract

This review illustrates how a random observation at the laboratory bench has helped pave the way towards the development of organelle-targeted pharmaceutical nanocarriers. A fortuitous discovery in the mid 1990s involving the self-assembly of a molecule, known to accumulate inside mitochondria, has lead to the development of subcellular nanocarriers suited for the selective delivery of biologically active molecules to mitochondria inside living mammalian cells. Applications for mitochondria-specific drug and DNA delivery are described, the current state-of-the-art of mitochondrial drug targeting technology is reviewed, and its future perspectives are discussed.

A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

“…The results presented herein constitute the first report of the use of a mitochondrial RNA aptamer modified nanocarrier system to regulate intracellular trafficking, although lipophilic and cationic peptide-based mitochondrial targeting has been reported in previous studies 12,19,[33][34][35] . In this study, we determined the optimal dual-ligand system for a nanocarrier for achieving efficient cellular uptake and mitochondrial targeting (RP/R8-modified MITO-Porter).…”

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

“…Thus, researchers dealing with mitochondrial drug delivery systems are encouraged to develop such therapeutic strategies based on the in vivo mitochondrial delivery of therapeutics. Various types of mitochondrial delivery systems have been reported during the past decades [4][5][6][7][8], but only a limited number of these approaches have the potential for use in mitochondrial therapy. These strategies face many problems including cell internalization, size limitations and the physicochemical properties of the cargo, modification of a functional device and the denaturation of the cargo [5,9,10].…”

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

“…However, their utility has not yet been realized because mitochondrial gene delivery technology is the bottleneck. Even through in vitro experiments have been reported, actual studies of mitochondrial gene delivery are very few [8][9][10][11]. The use of a variety of applications for nuclear gene delivery in vitro/in vivo have been reported [11][12][13][14][15][16], in attempts to accelerate progress in the field of nuclear gene therapy.…”