Novel Strategies for Disrupting Cancer-Cell Functions with Mitochondria-Targeted Antitumor Drug-Loaded Nanoformulations

Abstract

Any variation in normal cellular function results in mitochondrial dysregulation that occurs in several diseases, including cancer. Such processes as oxidative stress, metabolism, signaling, and biogenesis play significant roles in cancer initiation and progression. Due to their central role in cellular metabolism, mitochondria are favorable therapeutic targets for the prevention and treatment of conditions like neurodegenerative diseases, diabetes, and cancer. Subcellular mitochondria-specific theranostic nanoformulations for simultaneous targeting, drug delivery, and imaging of these organelles are of immense interest in cancer therapy. It is a challenging task to cross multiple barriers to target mitochondria in diseased cells. To overcome these multiple barriers, several mitochondriotropic nanoformulations have been engineered for the transportation of mitochondria-specific drugs. These nanoformulations include liposomes, dendrimers, carbon nanotubes, polymeric nanoparticles (NPs), and inorganic NPs. These nanoformulations are made mitochondriotropic by conjugating them with moieties like dequalinium, Mito-Porter, triphenylphosphonium, and Mitochondria-penetrating peptides. Most of these nanoformulations are meticulously tailored to control their size, charge, shape, mitochondriotropic drug loading, and specific cell-membrane interactions. Recently, some novel mitochondria-selective antitumor compounds known as mitocans have shown high toxicity against cancer cells. These selective compounds form vicious oxidative stress and reactive oxygen species cycles within cancer cells and ultimately push them to cell death. Nanoformulations approved by the FDA and EMA for clinical applications in cancer patients include Doxil, NK105, and Abraxane. The novel use of these NPs still faces tremendous challenges and an immense amount of research is needed to understand the proper mechanisms of cancer progression and control by these NPs. Here in this review, we summarize current advancements and novel strategies of delivering different anticancer therapeutic agents to mitochondria with the help of various nanoformulations.

Keywords: antitumor drugs; cancer; mitochondria targeting; mitochondriopathies; theranostic nanoparticles.