Table 2.
Summary of direct targeting strategies in recent years.
| Strategies for targeted therapy | Drugs or compounds used | The core of therapeutic strategy (Characteristics of mtDNA targeting) | Cancer | year | |
|---|---|---|---|---|---|
| Mukerabigwi et al. (Mukerabigwi et al., 2023) | Carrier system | TF@CNM + DOX | Design tumor and mitochondrial dual targeting multiprodrug to improve intracellular ros level and solve multi-drug resistance in cancers. | Breast carcinoma | 2023 |
| Yao et al. (Yao et al., 2023) | Carrier system | PIP-TPP (CCC-h1005) | CCC-h1005 can be used to treat many cervical cancers harboring high copies of the target variant | Cervical carcinoma | 2023 |
| Faria et al. (Faria et al., 2022) | Carrier system | PEI–DQA/TAT/pDNA, MTS-CPP/pDNA | Polymer and peptide delivery systems increased mitochondrial localization of targeted therapy. | Cervical carcinoma and lung cancer | 2022 |
| Luo et al. (Luo et al., 2022) | Carrier system | NP(Pt)@AL | The activity of thioredoxin reductase 1 inhibited by AL and the adducts of Pt (II) with mtDNA can costimulate ROS and reactivate the mitochondrial pathway of apoptosis. | Ovarian carcinoma | 2022 |
| Tsuji et al. (Tsuji et al., 2022) | Carrier system | novel PIP-TPP (CCC-021-TPP) | CCC-021-TPP caused cell senescence, accompanied by significant induction of anti-apoptotic BCL-XL | NSCLC | 2022 |
| Mondal et al. (Mondal et al., 2022) | Direct bonding | Ym155 | Ym155 binds mtDNA leading to mitochondrial dysfunction, including a decrease in OXPHOS and TCA cycle intermediates, and an increase in mitochondrial permeability. | Lung cancer | 2022 |
| Wang et al. (Wang et al., 2022c) | Metal complex | Zn (II)–cryptolepine–cyclen | It showed efficient plasmid DNA intercalation, and has a high binding affinity to mtDNA to cleave DNA, further causing mitochondrial damage, and can be used for cisplatin resistance | Lung cancer | 2022 |
| Echevarría et al. (Echevarría et al., 2022) | Metal complex, PDT | A family of Ir (III) complexes | Complexes [1a] Cl and [3a] Cl were able to cause severe cleavage on mtDNA, resulting in the inhibition of the expression of mitochondrial genes. | Prostate cancer and melanoma | 2022 |
| Bajpai et al. (Bajpai et al., 2022b) | Metal complex | Cholesterol-based chimeric nanoparticles consisting of cisplatin, camptothecin, and tigecycline | Particles localized efficiently into the mitochondria of cancer cells within 6 h, simultaneously impairing mtDNA, mt-Top1, and mitochondrial ribosomes. | Breast carcinoma, cervical carcinoma and lung cancer | 2022 |
| Jiang et al. (Jiang, Guo, et al., 2021) | Activate immunity, metal complexes | MSN-Ru2+/Fe2+ | MSN-Ru2+/Fe2+ could enter mitochondria to bind with mtDNA due to the lipophilic and DNA affinity of Ru2+ complex. Oxidative mtDNA is able to escape from the tumor cells and results in the reactivated immunoresponse of macrophages against cancer cells. | Pancreatic cancer | 2021 |
| Muhammad et al. (Muhammad et al., 2021) | Carrier system | c,c,t -[Pt-(NH3)2Cl2 (TPP) (Dox)] (PPD) | Enhanced mitochondrial localization and overcoming cisplatin resistance | Breast carcinoma | 2021 |
| Koshikawa et al. (Koshikawa et al., 2021) | Increase ROS, carrier system | A five-ring PIP-TPP | It localized in the mitochondria in HeLamtA3243G cells and induced mitochondrial ROS production, mitophagy and apoptosis in a mutation-specific fashion | Cervical carcinoma | 2021 |
| Zhang et al. (Zhang et al., 2021) | PTT, PDT | IR780@Pt NPs | Massive ROS generation and photothermal effects under 808 nm laser irradiation resulted in MMP loss, significantly reduced cellular ATP production, decreased cellular GSH levels, mtDNA damage, and mitochondrial dysfunction. | Osteosarcoma and cervical carcinoma | 2021 |
| Nair et al. (Nair et al., 2020) | Carrier system | A folic acid anchored p-sulfo-calix [4] arene capped hollow gold nanoparticles was meticulously loaded with Dox and Mt-Dox. | Overcomed off-target effects and eradicated both nDNA and mtDNA | Cervical carcinoma and lung cancer | 2020 |
| Chen et al. (Chen et al., 2020) | Carrier system | Choil-TPP | It could inhibit the transcription of mtDNA and damage mtDNA. | pancreatic cancer | 2020 |
| Yang et al. (Yang et al., 2020) | Carrier system, PTT | Pt (IV)-NPs contain IR780 | Pt (IV)-NPs could markedly facilitate cancer-specific mitochondrial targeting, inducing mitochondrial dysfunction and mtDNA damage, thus greatly increasing the Pt accumulation in cisplatin resistant cancer cells. | Lung cancer | 2020 |
| Liu et al. (Liu et al., 2020) | Direct bonding | Pentamidine | Pentamidine targets AT sequences in mtDNA, resulting in decreased transcription levels of mitochondrial coding genes, decreased mtDNA, and changes in mitochondrial morphology and function | Prostate cancer | 2020 |
| Qin et al. (Qin et al., 2020) | Metal complex | Cyclometalated iridium (III) complexes | Ir complexes induced an increase in intracellular ROS levels, a reduction in ATP production, mtDNA damage, an increase in lipid eroxidation levels, and proteasomal activity inhibition | Lung cancer | 2020 |
| Li et al. (Li, Wu, et al., 2020) | Metal complex, PDT | Dinuclear Ir(III)-containing luminescent metallohelices | It had stronger mtDNA binding affinity and better PDT effect. And mtDNA were cleaved by the generated intracellular 1O2. | Breast carcinoma and lung cancer | 2020 |
| Cao et al. (Cao et al., 2019) | Metal complex | Ir3: [Ir (dfppy)2 (dppz)](PF6); Ir4: [Ir (ptz)2 (dppz)](PF6) | Complexes Ir3 and Ir4 bound to mtDNA, intercalated to mtDNA in situ and induced mtDNA damage, resulting in decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status | Lung cancer | 2019 |
| Chen et al. (Chen et al., 2018) | Carrier system | peptide nucleic acids coupled with TPP | It targeted the D-loop regulatory region of mtDNA.TPP is a DLC for mitochondrial targeting, and PNA can bond to DNA and RNA targets efficiently | Lung cancer | 2018 |
| Wang et al. (Wang et al., 2018) | Carrier system, PTT | Nanoparticles: a core–shell –SS–shell architecture are composed of a core of Fe3O4 colloidal nanocrystal clusters, an inner shell of PDA functionalized with TPP, and an outer shell of methoxy poly (ethylene glycol) linked to the PDA by disulfide bonds. | The magnetic core can increase the accumulation of nanoparticles at the tumor site. A photothermal effect is generated from the PDA photosensitizer using NIR, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded Dox can enter the mitochondria and subsequently damage the mtDNA. | Melanoma | 2018 |
| Hu et al. (Hu et al., 2017) | Carrier system, PCT | UCNP core combined with mesoporous silica and Ru2+ complex. | Under NIR irradiation, the accumulated H2O2 in intratumoral mitochondrion will react with Fe2+ to efficiently generate localized –OH radicals which cause mtDNA damage. | Liver cancer | 2017 |
| Yang et al. (Yang et al., 2017) | Direct bonding, PDT | D112 | D112 bound to mtDNA, and induced mtDNA damage, ROS production and complex I inhibition. | Breast carcinoma | 2017 |
| Pokrzywinski et al. (Pokrzywinski et al., 2016) | Carrier system | mitoTEMPOL, mitoquinone and mitochromanol-acetate conjugated to TPP+ | Reduced mitochondrial function by affecting mtDNA integrity and oxidative respiration. | Breast carcinoma and lung cancer | 2016 |