Table 1 Nanodrugs targeting mitochondria for breast cancer treatment
Drugs | Formation | Targets | Methods |
|---|---|---|---|
engineered mitochondrial targeted delivery system | Co-delivery of a natural K-channel agonist (Dinitrogen oxide, DZX) and an artificial K-channel molecule (5F8) via an amphiphilic mitochondria-targeted polymer (TMP) | potassium ion (K) channels | Selective delivery of drugs to cancer cell mitochondria specifically activates natural potassium channels and assembles artificial K-selective ion channels, thereby causing K influx to disrupt intracellular ion homeostasis |
TNBC-specific targeted nano delivery agents | cRGD-labelled magnetic liposomes (T-LMD) with oleic acid-coated iron oxide nanoparticles (MN-OA) and doxorubicin (Dox) | iron/lipid metabolism pathway | Iron death nano-inducer (T-LMD) leads to membrane damage through enhanced ROS production, LDH and HMGB1 release while inducing mitochondrial alterations and enhanced DNA double-strand breaks |
ATO/SRF@BSA | Developed by loading sorafenib and atovaquone into bovine serum albumin | inhibiting the glutathione peroxidase 4 (GPX4)-GSH pathway and downregulating the DHODH-coenzyme Q (CoQH2) defense mechanism | Promotes accumulation of lipid peroxides in mitochondria and inhibits adenosine triphosphate (ATP) and pyrimidine nucleotide synthesis to inhibit cancer cell self-repair and enhance cell death. |
LND-PLGA/TPS/DSSR NPs | Clonidamine (LND) was encapsulated in PLGA nanoparticles (NPs) encapsulated with mitochondria-targeted short chains (TPP-TPGS, TPS) and tumour-targeted long chains (DSPE-S-S-PEG2000-R6RGD, DSSR) | amaging mitochondria and releasing apoptosis-related proteins | Improving efficacy and bioavailability and reducing hepatotoxicity of LND |
Ru-TPE-PPh3 | Synthesis via copper-catalysed cycloaddition of ruthenium nitride with alkynyl groups (CuAAC) | Excessive generation of reactive oxygen species (ROS) | Loss of mitochondrial membrane potential (MMP) and reduced adenosine triphosphate (ATP) production and onset of mitochondrial autophagy with autophagic flux blockage |
COMET | Mitochondrial network disruption (MiND) nanoparticles (NPs) loaded with anti-MFN2 peptide, clindamycin and Bam7 | Manipulation of intracellular communication and organelle fusion | Lowering the apoptotic threshold of MDR cells with MiND NPs, then inducing endoplasmic reticulum-mediated unfolded protein response (UPR) by stressing MDR cells with clindamycin, and finally inducing mitochondrial apoptosis with Bam7, a specific bcl-2 Bax activator. |
9S1R nullomer peptide | 9S1R peptide using alginate as a carrier | Mitochondrial TCA cycle/oxidative phosphorylation | Induction of mitochondrial structural and functional changes leading to deceleration of tumor metabolism |
RP7 | An antagonist peptide of the receptor for advanced glycosylation end products (RAGE) | RAGE | Inhibited the phosphorylation of ERK1/2, IKKα/β, IKBα and p65, blocked the NF-κB pathway, decreased the protein expression of Bcl-2 and HMGB1, and promoted the release of cytochrome C from mitochondria into the cytoplasm. Activated apoptosis in TNBC cells and inhibited epithelial-mesenchymal transition (EMT). |