Table 1.
Summary of mitochondria-targeting particles.
| Name | Materials/formulation | Cargo | Most advanced preclinical/ clinical research progress |
|---|---|---|---|
| Liposome-like vesicles | |||
| DQAsomes | Dequalimium chloride† | DNA [34–37,39] | In vitro (human) |
| Liposomes | |||
| Antiresistant epirubicin mitosomes | EPC:DC-chol HCl:PEG2000-DSPE:dequalimium† (in a 60:25:5:15 µmol ratio) | Epirubicin and amlodipine [40] | In vivo |
| Mitochondrial targeting daunorubicin plus quinacrine liposomes | EPC:chol:PEG2000-DSPE:dequalinium† (in a 55:25:3.5:8 µmol ratio) | Daunorubicin and quinacrine [41] | In vivo |
| Mitochondrial targeting topotecan-loaded liposomes | EPC:chol:PEG2000-DSPE:TPGS1000dequalinium† (in a 60:29:2:2:7 µmol ratio) | Topotecan [42] | In vivo |
| Mitochondrial targeting resveratrol liposomes | EPC:chol:DQA†-PEG2000-DSPE (in a 65:20:4.35 µmol ratio) | Resveratrol [44] | In vivo |
| Targeting lonidamine liposomes and epirubicin liposomes | EPC:TPGS1000:DQA†-PEG2000-DSPE (in a 90:5:5 µmol ratio) | Epirubicin and/or lonidamine [45] | In vivo |
| Targeted nanocarrier | DOPC:chol:STPP† (in a 83.5:15:1.5% of mole) | Ceramide [49] | In vivo |
| Paclitaxel-loaded STPP liposomes | EPC:chol:STPP† (in a 69:30:1 molar ratio) | Paclitaxel [50] | In vitro |
| TPP-PEG-PE modified liposomes | EPC:chol:TPP†-PEG-PE (in a 62:30:8% of mole) | Paclitaxel [51] | In vivo |
| Sclareol-loaded mitochondria-targeted liposomes | EPC:DPPG:STPP† (in a 8.87:0.1:0.136 molar ratio) | Sclareol [52] | In vitro (human) |
| Targeting paclitaxel liposomes | EPC:chol:TPGS1000-TPP† (in a 88:3.5:8.5 molar ratio) | Paclitaxel [53] | In vivo |
| Mitochondriotropic liposomes | Crude mitochondrial fraction/enriched lipid mitochondrial fraction | DNA [54] | In vitro (murine) |
| MITO-Porter | DOPE:sphingomyelin†:STR-R8† or DOPE:phosphatidic acid†: STR-R8† (in a 9:2:1 molar ratio) | GFP [55], propidium iodide [56] | In vitro (human) |
| DF-MITO-Porter | Inner envelope – DOPE:sphingomyelin†:CHEMS:STR-R8 (in a 9:2:1:1 molar ratio) or DOPE:phosphatidic acid:STR-R8 (in a 9:2:1 molar ratio); outer envelope – DOPE:phosphatidic acid:STR-R8 (in a 7:2:1 molar ratio) | DNAse I protein [58,60] | In vitro (human) |
| STR-S2-modified DF-MITO-Porter | Inner envelope – DOPE:sphingomyelin†:CHEMS (in a 9:2:1 molar ratio), STR-S2 was added with 10 mol% of lipid; outer envelope – DOPE:phosphatidic acid:STR-R8:chol-GALA (in a 7:2:1:0.1 molar ratio) | Oligo DNA [57] | In vitro (human) |
| Biodegradable polymeric particles | |||
| Mitochondria-targeted blended NPs | PLGA-b-PEG-TPP† blended with PLGA-b-PEG-OH or PLGA-COOH | Lonidamine, α-tocopheryl succinate, curcumin and 2,4-dinitrophenol [64] | In vitro (human) |
| Apoptosis-targeted HDL-mimicking NPs (TPP-HDL-apoA-1-QD NPs) | Core: PLGA, cholesteryl oleate, PLGA-b-PEG-QD; shell: DSPE-PEG-COOH, stearyl-TPP† | Contrast agent (QD in particle’s core) and apoA-1 mimetic 4F peptide (on the shell) [71] | In vitro (human) |
| Mitochondria-targeting ZnPc NPs (T-ZnPC-NPs) | PLGA-b-PEG-TPP† | Zinc(II) phthalocyanine [72] | In vitro (human) |
| Metal particles | |||
| Multilayered polypeptide-AuNP assembly (Au@CP/SA) | Core: Au NPs; shell: biotinylated CALNN-based peptide, tetrameric streptavidin and biotinylated bioactive molecules | KLA cytotoxic peptide (KLAKLAK)2 [76] | In vitro (human) |
| AuNP–Simdax® (Orion Corporation, Espoo, Finland) conjugate | Au NPs | Simdax (levosimendan) [79] | In vivo |
| TiO2-DNA | TiO2 NPs | Oligo nucleotides [80] | In vitro (human) |
| CO NPs | CO NPs | Not applicable [81] | In vitro (human) |
| MoO3 | MoO3 with dopamine-TPP† ligand | Not applicable [83] | In vitro (human) |
Substance used as a mitochondrial targeting or mitochondrial fusing agent. All in vivo experiments were conducted using a murine model.
CALNN: Cys-Ala-Leu-Asn-Asn; CHEMS: Cholesteryl hemisuccinate (5-cholesten-3-ol 3-hemisuccinate); Chol: Cholesterol; DC-chol HCl: 3β-[N-(N’, N’-dimethylaminoethane)-carbomoyl] cholesterol hydrochloride; CP: CALNN-based peptide; DF: Dual function; DQA: Dequalinium; DOPC: Dioleoyphosphatidyl choline; DOPE: 1,2-Dioleoyl-sn-glycero-3-phosphatidyl ethanolamine; DPPG: Dipalmitoylphosphatidylglycerol; DSPE: 1,2-Distearoyl-sn-glyceo-3-phosphoethanolamine; EPC: Egg phosphatidylcholine; GALA: WEAALAEALAEALAEHLAEALAEALEALAA-NH2; GFP: Green fluorescent protein; HDL: High-density lipoprotein; KLA: Lys-Leu-Ala; MITO: Mitochondrial; NP: Nanoparticle; PE: Phosphatidylethanolamine; PLGA: Poly(lactic-co-glycolic acid); QD: Quantum dot; SA: Streptavidin; STPP: Stearyl-triphenylphosphonium; STR-S2: Stearyl-Dmt-D-Arg-FK-Dmt-D-Arg-FK-NH2; STR-R8: Stearyl octaarginine; T-ZnPC-NP: Mitochondria-targeting zinc (II) phthalocyanine nanoparticle; TPGS1000: D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E polyethylene glycol succinate); TPP: Triphenylphosphonium cation; ZnPC: Zinc (II) phthalocyanine.