Mitochondria-targeted delocalized lipophilic cation complexed with human serum albumin for tumor cell imaging and treatment

Mitochondria targeting drugs for neurodegenerative diseases—Design, mechanism and application

“…To achieve mitochondria targeting, many strategies have been proposed and verified to be feasible ( Fig. 1 and Table 1 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ).

Figure 1 The structures of small molecules and peptides with mitochondria targeting ability.

…”

“… Chemical nature Group Molecule Targeting mechanism Advantage/disadvantage Ref. Small molecule TPP + Mito-Q; Mito-Vit-E; Mito-TEMPOL; TPP + functionalized liposomes; Ceria nanoparticle; Silica nanoparticles Positive charge and lipid solubility Easy to synthesis/cytotoxicity for drug delivery 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 Small molecule Pyridinium salt 5BMF@HSA complex Positive charge and lipophilic, HSA increasing water solubility Easy to synthesis, tunable luminescence/cytotoxicity for drug delivery 16 Small molecule DQA QDAsomes Amphipathic Easy to synthesis, cytotoxicity for drug delivery/low endosomal escape ability and transfection efficiency 17 , 18 Small molecule Ru/Ir Ru/Ir complexes Positive charge and lipophilic Cytotoxicity for cancer therapy/multimodal therapy 19 , 20 Peptide S-S peptides SS-02, SS-31 Positive charge and lipophilic Hypotoxicity, antioxidant/complex 21 Peptide MPP MPP Positive charge and lipophilic Hypotoxicity, tunability, desirable pharmacokinetic profiles/complex synthesis 22 , 23 CPMs CPM CPM1, CPM2, CPM3 Amphipathic Efficient and universal delivery of cargos/complex synthesis 24 Mito-Porter Octa arginine (DF)-Mito-Porter, ASO-Mito-Porer, DOX-Mito-Porter Lipid compo...…”

Cancer molecular biology and strategies for the design of cytotoxic gold(i) and gold(iii) complexes: a tutorial review

“…173,187 Another approach to targeting the mitochondria of cancer cells is the development of a diverse group of compounds called delocalized lipophilic cations (DLCs). 195 These compounds, which include metal chelates, 196 are characterized by elevated partition coefficient values to readily pass lipid membranes and a delocalized positive charge, 197 which allows them to be driven towards negatively charged species. In fact, the mitochondria of cancer cells have elevated mitochondrial membrane potential (Δψ m ) due to an increased rate of ATP production.…”

Medicinal Chemistry Targeting Mitochondria: From New Vehicles and Pharmacophore Groups to Old Drugs with Mitochondrial Activity

“…Researchers have synthesized F16 derivatives with substitutions in the indole ring of F16 to produce molecules with improved selectivity and antitumor activity, such as a 5BMF derivative that displays cytotoxic effects in vitro and antitumor effects in vivo. Furthermore, 5BMF has been useful as a fluorescent probe for tumor imaging capacity [ 97 ]. This molecule was complexed with human serum albumin (HSA) to form the 5BMF@HSA complex, which improved the fluorescence intensity of 5BMF and increased its solubility by nearly 3.4-fold.…”

“…Both 5BMF and 5BMF@HSA produced a decrease in subcutaneous U87MG tumors, but the complex showed slightly better tumor growth suppression than 5BMF group alone. Thus, the 5BMF@HSA complex has potential applications in both cellular imaging and antitumor therapeutics [ 97 ].…”