| Literature DB >> 30505656 |
Gantumur Battogtokh1, Yeon Su Choi1, Dong Seop Kang1, Sang Jun Park1, Min Suk Shim2, Kang Moo Huh3, Yong-Yeon Cho1, Joo Young Lee1, Hye Suk Lee1, Han Chang Kang1.
Abstract
Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo, further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.Entities:
Keywords: (Fx, r)3, (l-cyclohexyl alanine-d-arginine)3; 4-AT, 4-amino-TEMPO; 5-FU, 5-Fluorouracil; AD, Alzheimer׳s disease; AIE, aggregation-induced emission; ATP, adenosine triphosphate; Anticancer agents; Antioxidants; Arg, arginine; Aβ, beta amyloid; BODIPY, boron-dipyrromethene; C-dots, carbon dots; CAT, catalase; COX, cytochrome c oxidase; CZBI, carbazole and benzo[e]indolium; CoA, coenzyme A; DDS, drug delivery system; DEPMPO, 5-(diethylphosphono)-5-methyl-1-pyrroline N-oxide; DIPPMPO, 5-(diisopropoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide; DQA, dequalinium; Direct conjugation; Dmt, dimethyltyrosine; EPR, enhanced permeability and retention; F16, (E)-4-(1H-indol-3-ylvinyl)-N-methylpyridinium iodide; GPX, glutathione peroxidase; GS, gramicidin S; HTPP, 5-(4-hydroxy-phenyl)-10,15,20-triphenylporphyrin; IMM, inner mitochondrial membrane; IMS, intermembrane space; IOA, imidazole-substituted oleic acid; LA, lipoic acid; LAH2, dihydrolipoic acid; Lys, lysine; MET, mesenchymal-epithelial transition; MLS, mitochondria localization sequences; MPO, myeloperoxidase; MPP, mitochondria-penetrating peptides; MitoChlor, TPP-chlorambucil; MitoE, TPP-vitamin E; MitoLA, TPP-lipoic acid; MitoQ, TPP-ubiquinone; MitoVES, TPP-vitamin E succinate; Mitochondria-targeting; Nit, nitrooxy; NitDOX, nitrooxy-DOX; OMM, outer mitochondrial membrane; OXPHOS, oxidative phosphorylation; PD, Parkinson׳s disease; PDT, photodynamic therapy; PET, photoinduced electron transfer; PS, photosensitizer; PTPC, permeability transition pore complex; Phe, phenylalanine; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; SS peptide, Szeto-Schiller peptides; Sensing agents; SkQ1, Skulachev ion-quinone; TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl; TPEY-TEMPO, [2-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-ylimino)-ethyl]-triphenyl-phosphonium; TPP, triphenylphosphonium; Tyr, tyrosine; VDAC/ANT, voltage-dependent anion channel/adenine nucleotide translocase; VES, vitamin E succinate; XO, xanthine oxidase; mitoTEMPO, (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium); mtCbl, (Fx,r)3-chlorambucil; mtDNA, mitochondrial DNA; mtPt, mitochondria-targeting (Fx,r)3-platinum(II); nDNA, nuclear DNA; αTOS, alpha-tocopheryl succinate.
Year: 2018 PMID： 30505656 PMCID： PMC6251809 DOI： 10.1016/j.apsb.2018.05.006
Source DB: PubMed Journal: Acta Pharm Sin B ISSN： 2211-3835 Impact factor: 11.413