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Photothermally Triggered Copper Payload Release for Cuproptosis-Promoted Cancer Synergistic Therapy.Angewandte Chemie (International Ed. in... Mar 2023Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue...
Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper-induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN-Cu/PEG/DSF) to realize on-demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN-Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano-therapeutic platforms.
Topics: Humans; Antineoplastic Agents; Cell Line, Tumor; Copper; Disulfiram; Ditiocarb; Neoplasms; Apoptosis
PubMed: 36585379
DOI: 10.1002/anie.202213922 -
JAMA Aug 1991
Topics: Antiviral Agents; Ditiocarb; HIV Infections; Humans
PubMed: 1650850
DOI: No ID Found -
Lancet (London, England) Sep 198883 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium-diethyldithiocarbamate... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
83 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium-diethyldithiocarbamate (ditiocarb sodium, 'Imuthiol') (10 mg/kg body weight given orally once a week) against placebo. Each arm of the trial lasted 16 weeks. The disease did not progress to CDC-defined acquired immunodeficiency syndrome in the ditiocarb group but did so in 4 patients in the placebo group (3 between week 0 and 16, 1 between week 17 and 32). Ditiocarb was also associated to a significantly greater extent than placebo with relief of constitutional symptoms, improvement in clinical status (including shrinkage of enlarged spleen and lymph nodes), and improvement in immune function (as measured by CD4+ cell count and skin test reactivity). When placebo was replaced by ditiocarb, similar improvements were observed, whereas symptoms slowly reappeared and CD4+ cell levels progressively declined when ditiocarb treatment was replaced by placebo.
Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Clinical Trials as Topic; Ditiocarb; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; HIV; HIV Seropositivity; Humans; Leukocyte Count; Lymphocytes; Random Allocation; Skin Tests
PubMed: 2901566
DOI: 10.1016/s0140-6736(88)90184-5 -
Nursing Times
Clinical Trial Randomized Controlled Trial
Topics: Adolescent; Adult; Ditiocarb; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Opportunistic Infections
PubMed: 1851986
DOI: No ID Found -
Current HIV Research May 2009
Topics: Anti-HIV Agents; Diet; Ditiocarb; HIV Infections; Humans; Treatment Failure
PubMed: 19442119
DOI: 10.2174/157016209788348038 -
Nanomedicine : Nanotechnology, Biology,... Feb 2021Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of...
Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of disulfiram. But the hydrophobic property of CuET limits its use in vivo, and an appropriate drug delivery system needs to be developed. Ultrasmall melanin nanoparticle (M-Dot) with excellent biosafety and biocompatibility properties has been synthesized in our previous studies. Herein we prepared CuET loaded with M-Dots through hydrophobic interaction, which could enhance the water solubility significantly. After the administration of M-Dots-CuET in mice tumor models, the nanoparticles showed good tumor accumulation as evidenced by the enhanced photoacoustic signal in tumor regions. M-Dots-CuET also displayed excellent tumor inhibition capability, and the tumor growth inhibition value (TGI) was 45.1%. When combined with photothermal therapy, the TGI reached up to 78.6%. In summary, M-Dots-CuET provide a new potential strategy for cancer theranostics.
Topics: Animals; Cell Line, Tumor; Copper; Disulfiram; Ditiocarb; Female; Hyperthermia, Induced; Melanins; Mice; Mice, Inbred BALB C; NIH 3T3 Cells; Nanoparticles; Neoplasms; Photoacoustic Techniques; Phototherapy; Theranostic Nanomedicine
PubMed: 33227540
DOI: 10.1016/j.nano.2020.102340 -
The Journal of Antimicrobial... Dec 1998Clinical resistance of Trichomonas vaginalis to metronidazole is best correlated with MIC values measured under aerobic conditions. Under these conditions both... (Comparative Study)
Comparative Study
Activity of disulfiram (bis(diethylthiocarbamoyl)disulphide) and ditiocarb (diethyldithiocarbamate) against metronidazole-sensitive and -resistant Trichomonas vaginalis and Tritrichomonas foetus.
Clinical resistance of Trichomonas vaginalis to metronidazole is best correlated with MIC values measured under aerobic conditions. Under these conditions both disulfiram (bis(diethylthiocarbamoyl)disulphide), and its first mammalian metabolite, ditiocarb (diethyldithiocarbamate), showed high levels of activity against metronidazole-sensitive (disulfiram MIC, 0.1-0.7 microM; ditiocarb MIC, 0.3-9 microM) and -resistant (MICs 0.2-1.3 microM and 1.2-9 microM respectively) isolates. Tritrichomonas foetus was also sensitive-the MICs for seven metronidazole-sensitive isolates were 0.1-1.0 microM for disulfiram and 1.0-6.9 microM for ditiocarb; those for two highly metronidazole-resistant strains were 0.3-1.3 microM and 0.6-6 microM respectively. Under anerobic conditions most strains became highly resistant to both compounds. Surprisingly, disulfiram was consistently more active than ditiocarb.
Topics: Aerobiosis; Anaerobiosis; Animals; Antiprotozoal Agents; Antitrichomonal Agents; Disulfiram; Ditiocarb; Drug Resistance; Metronidazole; Trichomonas vaginalis; Tritrichomonas foetus
PubMed: 10052908
DOI: 10.1093/jac/42.6.817 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogens; Chelating Agents; Ditiocarb; Herbicides; Humans; Neoplasms; Occupational Exposure
PubMed: 21863099
DOI: No ID Found -
Substance and Alcohol Actions/misuse 1980
Review
Topics: Alcoholism; Aldehyde Dehydrogenase; Aldehyde Oxidoreductases; Animals; Behavior; Carbon Disulfide; Cyanamide; Diethylamines; Disulfiram; Ditiocarb; Drug Implants; Glutamine; Humans; Metronidazole
PubMed: 6275559
DOI: No ID Found -
Journal of Pharmaceutical Sciences Apr 1993The kinetic profile for the decomposition of ditiocarb sodium salt in aqueous solution was achieved with UV-visible absorption spectrometry. The kinetic profile...
The kinetic profile for the decomposition of ditiocarb sodium salt in aqueous solution was achieved with UV-visible absorption spectrometry. The kinetic profile indicates that the decomposition reaction is hydrogen ion-catalyzed over the entire 4-10 pH range and enables the determination of the value of the acid-base equilibrium constant (Ka = 4.0.10(-4) at 5 degrees C). Decomposition of ditiocarb produces volatile carbon disulfide, exclusive of hydrogen sulfide, as shown with electrochemical methods. This feature is of interest from a toxicological point of view.
Topics: Ditiocarb; Hydrogen-Ion Concentration; Kinetics; Solutions; Volatilization
PubMed: 8385710
DOI: 10.1002/jps.2600820409