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.

Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics

“…The approach of a drug delivery system even up to the organelle level (third level drug targeting) with the aid of different nanoformulations has revolutionized the therapeutic approach for different diseases, including cancer. 187 …”

Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy

“…In the meantime, directed from these unique properties of mitochondria, researchers take advantage of them as active targeting mechanisms for designing mitochondria-targeted nanocarriers. Surface engineering of polymeric nanoparticles with lipophilic cations, peptides, or aptamers can infuse them with mitochondriotropic properties, to exert ideal cancer therapeutic effects (Allemailem et al, 2021). In this section, we will summarize the various strategies adopted in the design of polymeric nanoparticles for mitochondria-targeted cancer therapy.…”

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

“…Nanotechnology could help overcome several main limitations of conventional chemotherapy and photodynamic and/or photothermal therapies through tissue/cell-specific targeting, controlled release to specific subcellular organelles, and prolonged half-life in circulation. In view of the aforementioned critical role of mitochondria in controlling the fate of cells and the fact that there are prior comprehensive reviews on mitochondria-targeting materials/molecules [ 36 , 37 , 38 ] and mitochondrial biology [ 38 , 39 ], this mini-review surveys mitochondria-targeting nanoparticle drug delivery and its potential and challenges for advancing photodynamic, photothermal, and chemotherapies.…”