89996-00-9Relevant articles and documents
Mitochondria-specific oxygen probe based on iridium complexes bearing triphenylphosphonium cation
Murase, Tokiko,Yoshihara, Toshitada,Tobita, Seiji
, p. 262 - 263 (2012)
Organelle-selective oxygen probe BTP-Mito was designed and synthesized to selectively target mitochondria. BTP-Mito, which is an iridium complex bearing a triphenylphosphonium cation, exhibited selective mitochondria localization in HeLa cells. The phosphorescence of BTP-Mito was significantly quenched by molecular oxygen in living cells, demonstrating that BTP-Mito can be used as mitochondria-specific oxygen sensor.
A Mitochondria-Targeted Cryptocyanine-Based Photothermogenic Photosensitizer
Jung, Hyo Sung,Lee, Jae-Hong,Kim, Kyutae,Koo, Seyoung,Verwilst, Peter,Sessler, Jonathan L.,Kang, Chulhun,Kim, Jong Seung
, p. 9972 - 9978 (2017)
Cryptocyanine-based probes exhibit highly efficient photothermal conversion and represent a new class of photothermal agents for use in photothermal therapy (PTT). With the thermal susceptibility of mitochondria in mind, we have prepared a mitochondria-targeted, NIR-absorbing cryptocyanine probe (Mito-CCy) and evaluated its photophysical properties, photothermal conversion efficiency, biological compatibility, cytotoxicity, and mitochondrial localization in HeLa cells. Upon subjecting 0.5 mL of a PBS buffer solution (10 mM, pH 7.4, containing 50% DMSO) of Mito-CCy (0.5 mM) to 730 nm laser irradiation at 2.3 W/cm2, the temperature of the solution increased by 13.5 °C within 5 min. In contrast, the corresponding cryptocyanine (CCy) lacking the triarylphosphonium group gave rise to only an 3.4 °C increase in solution temperature under otherwise identical conditions. Mito-CCy also exhibited high cytotoxicity in HeLa cells when subject to photoirradiation. This light-induced cytotoxicity is attributed to the endogenous production of reactive oxygen species (ROS) induced under conditions of local heating. ROS are known to interfere with the mitochondrial defense system and to trigger apoptosis. By targeting the mitochondria, the present sensitizer-based photothermogenic approach is rendered more effective. As such, the system reported here represents the vanguard of what might be a new generation of organelle-targeted photothermal therapeutics.
Reversible color-changing fluorescent dye capable of targeting mitochondria in a solid state/solution as well as preparation method and application of fluorescent dye
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Paragraph 0061-0065, (2021/02/10)
The invention discloses a reversible color-changing fluorescent dye capable of targeting mitochondria in a solid state/solution, and belongs to the technical field of organic optical functional materials. The structural formula of the fluorescent dye is shown as a formula (I). The invention also discloses a preparation method and application of the reversible color-changing mitochondria-targetingfluorescent dye in a solid state/solution. According to the invention, a naphthalimide unit and two spiro-pyrane units are bonded for bonding, and then a triphenylphosphine salt unit is introduced tosynthesize the fluorescence resonance energy transfer type fluorescent dye capable of targeting a mitochondrial unit. Fluorescence resonance energy transfer type light-adjusting fluorescence reversible transformation can occur no matter in a liquid or solid medium or in a self solid state, so that the fluorescence color is obviously changed, and the fluorescent probe can be widely applied to biomarkers and fluorescence detection.
REAL-TIME FLUORESCENCE IMAGING SENSOR FOR MEASURING GLUTATHIONE IN ORGANELLE AND PREPARATION METHOD THEREFOR
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Paragraph 0053-0056, (2020/07/15)
The present invention relates to a real-time fluorescence imaging sensor for measuring glutathione in cell organelles and a method for fabricating the same. More specifically, the present invention relates to a novel compound for measuring glutathione in cell organelles, a method for preparing the novel compound, a real-time fluorescence imaging sensor for measuring glutathione in cell organelles, which comprises the novel compound, a method for fabricating the imaging sensor, and a method of measuring glutathione in cell organelles by use of the imaging sensor. When the composition comprising the compound according to the present invention is used, it can measure the antioxidant activity of the organelle mitochondria or Golgi apparatus in living cells, particularly stem cells, and can screen highly active stem cells based on the results obtained by measuring the antioxidant activity of the cell organelle.
Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications
Guo, Yuda,Han, Guifang,Hou, Jingli,Liao, Yongfang,Liu, Yangping,Qian, Meng,Song, Yuguang,Wang, Xing,Ye, Zizhen
supporting information, p. 5473 - 5480 (2020/08/03)
Bacterial infection is a major threat to the health and life of humans due to the development of drug resistance, which is related to biofilm formation. Nitric oxide (NO) has emerged as an important factor in regulating biofilm formation. In order to harness the potential benefits of NO and develop effective antibacterial agents, we designed and synthesized a new class of NO hybrids in which the active scaffold benzothienoazepine was tagged with a nitroso group and further conjugated with quaternary ammoniums or phosphoniums. The temporal release of NO from these hybrids can be achieved by photoactivation. Interestingly, the NO release follows a pseudo-zero-order kinetics, which is easily determined by measuring the fluorescent benzothienoazepine or NO. Compared to the positive control ciprofloxacin, the NO hybrid with triphenyl phosphonium (TPP) exhibited more effective activity against S. aureus biofilm in darkness. Irradiation of the NO hybrid led to higher inhibition against S. aureus biofilm compared to the parental NO hybrid in darkness or the corresponding NO-released product, indicating the combined effect of NO and the NO-released product. Therefore, this new class of NO hybrids includes very promising antimicrobial agents and this work provides a new way for the design of highly effective antimicrobial agents. This journal is
Precise imaging of mitochondria in cancer cells by real-time monitoring of nitroreductase activity with a targetable and activatable fluorescent probe
Gu, Xianfeng,Tan, Jiahui,Wang, Rongchen,Xu, Ge,Zhao, Chunchang,Zhu, Ning,Zhu, Tianli
supporting information, p. 7761 - 7764 (2020/07/27)
An activatable and mitochondrial-targetable fluorescent probe was developed. This designed probe showed ratiometric fluorescence and light-up near-infrared emission responsiveness to nitroreductase, achieving precise imaging of mitochondria in cancer cells by real-time monitoring of nitroreductase activity.
Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes
Florès, Océane,Velic, Denis,Mabrouk, Nesrine,Betta?eb, Ali,Tomasoni, Christophe,Robert, Jean-Michel,Paul, Catherine,Goze, Christine,Roussakis, Christos,Bodio, Ewen
, p. 2255 - 2261 (2019/08/01)
A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure–activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.
Non-peptidic guanidinium-functionalized silica nanoparticles as selective mitochondria-targeting drug nanocarriers
Ahn, Junho,Lee, Boeun,Choi, Yeonweon,Jin, Hanyong,Lim, Na Young,Park, Jaehyeon,Kim, Ju Hyun,Bae, Jeehyeon,Jung, Jong Hwa
supporting information, p. 5698 - 5707 (2018/09/29)
We report on the design and fabrication of a Fe3O4 core-mesoporous silica nanoparticle shell (Fe3O4@MSNs)-based mitochondria-targeting drug nanocarrier. A guanidinium derivative (GA) was conjugated onto the Fe3O4@MSNs as the mitochondria-targeting ligand. The fabrication of the Fe3O4@MSNs and their functionalization with GA were carried out by the sol-gel polymerization of alkoxysilane groups. Doxorubicin (DOX), an anti-cancer drug, was loaded into the pores of a GA-attached Fe3O4@MSNs due to both its anti-cancer properties and to allow for the fluorescent visualization of the nanocarriers. The selective and efficient mitochondria-targeting ability of a DOX-loaded GA-Fe3O4@MSNs (DOX/GA-Fe3O4@MSNs) was demonstrated by a co-localization study, transmission electron microscopy, and a fluorometric analysis on isolated mitochondria. It was found that the DOX/GA-Fe3O4@MSNs selectively accumulated into mitochondria within only five minutes; to the best of our knowledge, this is the shortest accumulation time reported for mitochondria targeting systems. Moreover, 2.6 times higher amount of DOX was accumulated in mitochondria by DOX/GA-Fe3O4@MSNs than by DOX/TPP-Fe3O4@MSNs. A cell viability assay indicated that the DOX/GA-Fe3O4@MSNs have high cytotoxicity to cancer cells, whereas the GA-Fe3O4@MSNs without DOX are non-cytotoxic; this indicates that the DOX/GA-Fe3O4@MSNs have great potential for use as biocompatible and effective mitochondria-targeting nanocarriers for cancer therapy.
Unique Triphenylphosphonium Derivatives for Enhanced Mitochondrial Uptake and Photodynamic Therapy
Hu, Zhang,Sim, Ying,Kon, Oi Lian,Ng, Wai Har,Ribeiro, António J. M.,Ramos, Maria J.,Fernandes, Pedro A.,Ganguly, Rakesh,Xing, Bengang,García, Felipe,Yeow, Edwin K. L.
, p. 590 - 599 (2017/02/23)
In this study, unique methyl-functionalized derivatives (T?PP+) of the drug carrier triphenylphosphonium (TPP+) that exhibit significant enhancement of the accumulation of both the cation and its conjugated cargo in cell mitochondria are designed. We show that the presence of methyl group(s) at key positions within the phenyl ring results in an increase in the hydrophobicity and solvent accessible surface area of T?PP+. In particular, when the para position of the phenyl ring in T?PP+ is functionalized with a methyl group, the cation is most exposed to the surrounding environment, leading to a large decrease in water entropy and an increase in the level of van der Waals interaction with and partition into a nonpolar solvent. Therefore, stronger binding between the hydrophobic T?PP+ and mitochondrial membrane occurs. This is exemplified in a (hexachloro-fluorescein)-TPP+ conjugate system, where an ～12 times increase in the rate of mitochondrial uptake and a 2 times increase in photodynamic therapy (PDT) efficacy against HeLa and FU97 cancer cells are achieved when TPP+ is replaced with T?PP+. Importantly, nearly all the FU97 cells treated with the (hexachloro-fluorescein)-T?PP+ conjugate are killed as compared to only half the population of cells in the case of the (hexachloro-fluorescein)-TPP+ conjugate at a similar PDT light dosage. This study thus forms a platform for the healthcare community to explore alternative TPP+ derivatives that can act as optimal drug transporters for enhanced mitochondrially targeted therapies.
Mitochondrial-Targeting MET Kinase Inhibitor Kills Erlotinib-Resistant Lung Cancer Cells
Yang, Tianming,Ng, Wai Har,Chen, Huan,Chomchopbun, Kamon,Huynh, The Hung,Go, Mei Lin,Kon, Oi Lian
supporting information, p. 807 - 812 (2016/08/24)
Lung cancer cells harboring activating EGFR mutations acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) by activating several bypass mechanisms, including MET amplification and overexpression. We show that a significant proportion of activated MET protein in EGFR TKI-resistant HCC827 lung cancer cells resides within the mitochondria. Targeting the total complement of MET in the plasma membrane and mitochondria should render these cells more susceptible to cell death and hence provide a means of circumventing drug resistance. Herein, the mitochondrial targeting triphenylphosphonium (TPP) moiety was introduced to the selective MET kinase inhibitor PHA665752. The resulting TPP analogue rapidly localized to the mitochondria of MET-overexpressing erlotinib-resistant HCC827 cells, partially suppressed the phosphorylation (Y1234/Y1235) of MET in the mitochondrial inner membrane and was as cytotoxic and apoptogenic as the parent compound. These findings provide support for the targeting of mitochondrial MET with a TPP-TKI conjugate as a means of restoring responsiveness to chemotherapy.
