Emerging insights into mitochondria-specific targeting and drug delivering strategies: Recent milestones and therapeutic implications

Abstract

Mitochondria are a major intracellular organelle for drug targeting due to its functional roles in cellular metabolism and cell signaling for proliferation and cell death. Mitochondria-targeted treatment strategy could be promising to improve the therapeutic efficacy of cancer while minimizing the adverse side effects. Over the last decades, several studies have explored and focused on mitochondrial functions, which has led to the emergence of mitochondria-specific therapies. Molecules in the mitochondria are considered to be prime targets, and a wide range of molecular strategies have been designed for targeting mitochondria compared with that of the cytosol. In this review, we focused on the molecular mechanisms of mitochondria-specific ligand targeting and selective drug action strategies for targeting mitochondria, including those premised on mitochondrial targeting of signal peptides (MTS), cell-penetrating peptides (CPPs), and use of lipophilic cations. Furthermore, most research has concentrated on specific conjugation of ligands to therapeutic molecules to enhance their effectiveness. There are several variations for the ideal design and development for mitochondrial-targeted drugs, such as selecting a suitable ligand and linker targets. However, some challenges related to drug solubility and selectivity could be resolved using the nanocarrier system. Nanoparticles yield excellent advantages for targeting and transmitting therapeutic drugs, and they offer elegant platforms for mitochondria-specific drug delivery. We explain many of the advanced and proven strategies for multifunctional mitochondria-specific targets, which should contribute to achieving better anticancer therapies in a promising future.

Rocaglamide promotes the infiltration and antitumor immunity of NK cells by activating cGAS-STING signaling in non-small cell lung cancer

“…Mitochondria are involved in cancer progression and emerging as a promising therapeutic target for cancer therapy [28]. mtDNA can be released from the mitochondria into the cytoplasm and play a key role in inflammation and immunity [29], suggesting that mtDNA is a promising target for 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.…”

In-vitro pH-responsive release of imatinib from iron-supplement coated anatase TiO2 nanoparticles

“…Dysfunctional mitochondria promotes cancer cell invasion, cancer survival and anticancer drug resistance. Nowadays, mitochondria-targeted drug delivery systems are being mechanised making mitochondria—the prime target of new anticancer drugs 8 . Chen et al 9 reported that Imatinib induces mitochondria-assisted apoptosis and restricts the invasion of pigmented villonodular synovitis cells.…”