Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer

Abstract

The early understanding of mitochondria posited that they were 'innocent organelles' solely devoted to energy production and utilisation. Intriguingly, recent findings have outlined in detail the 'modern-day' view that mitochondria are an important but underappreciated drug target. Mitochondria have been implicated in the pathophysiology of many human diseases, ranging from neurodegenerative disorders and cardiovascular diseases to infections and cancer. It is now clear that normal mitochondrial function involves the building blocks of a cell to generate lipids, proteins and nucleic acids thereby facilitating cell growth. On the other hand, mitochondrial dysfunction reprograms crucial cellular functions into pathological pathways, and is considered as an integral hallmark of cancer. Therefore, strategies to target mitochondria can provide a wealth of new therapeutic approaches in the fight against cancer, by overcoming a number of problems associated with conventional pharmaceutical drugs, including low solubility, poor bioavailability and non-selective biodistribution. The combination of nanoparticles with 'classical' chemotherapeutic drugs to create biocompatible, multifunctional mitochondria-targeted nanoplatforms has been recently studied. This approach is now rapidly expanding for targeted drug delivery systems, and for hybrid nanostructures that can be activated with light (photodynamic and/or photothermal therapy). The selective delivery of nanoparticles to mitochondria is an elegant shortcut to more selective, targeted, and safer cancer treatment. We propose that the use of nanoparticles to target mitochondria be termed "mitoNANO". The present minireview sheds light on the design and application of mitoNANO as advanced cancer therapeutics, that may overcome drug resistance and show fewer side effects.

Graphical abstract

Fig. 1

Schematic showing mitochondria as a key driver and important therapeutic target of cancer. This figure shows the chaotic progression of events linked to cell death. Proton translocation derived by respiratory actions of complexes I, III and IV across the inner mitochondrial membrane mediates the generation of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and Pi. Oxidation of mitochondrial electron transfer chain by quinone oxidoreductase results in the reduction of coenzyme quinone (Q). Reduced Q generates cytochrome c (via complex III) which catalyses the reduction of molecular oxygen to water (via complex IV). Reactive oxygen species (ROS) generation derived from complex I along with accumulation of calcium ions facilitates the opening of mitochondrial permeability transition pore (MPTP) thereby resulting in programmed cell death.