Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.878
Filtrar
1.
Sci Rep ; 14(1): 5604, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453950

RESUMO

Control charts are a statistical approach for monitoring cancer data that can assist discover patterns, trends, and unusual deviations in cancer-related data across time. To detect deviations from predicted patterns, control charts are extensively used in quality control and process management. Control charts may be used to track numerous parameters in cancer data, such as incidence rates, death rates, survival time, recovery time, and other related indicators. In this study, CDEC chart is proposed to monitor the cancer patients recovery time censored data. This paper presents a composite dual exponentially weighted moving average Cumulative sum (CDEC) control chart for monitoring cancer patients recovery time censored data. This approach seeks to detect changes in the mean recovery time of cancer patients which usually follows Weibull lifetimes. The results are calculated using type I censored data under known and estimated parameter conditions. We combine the conditional expected value (CEV) and conditional median (CM) approaches, which are extensively used in statistical analysis to determine the central tendency of a dataset, to create an efficient control chart. The suggested chart's performance is assessed using the average run length (ARL), which evaluates how efficiently the chart can detect a change in the process mean. The CDEC chart is compared to existing control charts. A simulation study and a real-world data set related to cancer patients recovery time censored data is used for results illustration. The proposed CDEC control chart is developed for the data monitoring when complete information about the patients are not available. So, instead of doping the patients information we can used the proposed chart to monitor the patients information even if it is censored. The authors conclude that the suggested CDEC chart is more efficient than competitor control charts for monitoring cancer patients recovery time censored data. Overall, this study introduces an efficient new approach for cancer patients recovery time censored data, which might have significant effect on quality control and process improvement across a wide range of healthcare and medical studies.


Assuntos
Ditiocarb/análogos & derivados , Instalações de Saúde , Neoplasias , Humanos , Simulação por Computador , Tempo , Controle de Qualidade , Neoplasias/diagnóstico
2.
ACS Appl Mater Interfaces ; 16(7): 8484-8498, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38334265

RESUMO

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu2+ ions in situ to form the highly toxic bis(N,N-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu2+ to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu2+ are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86+ CD80+ cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.


Assuntos
Cadaverina/análogos & derivados , Cobre , Neoplasias , Humanos , Linhagem Celular Tumoral , Cobre/farmacologia , Cobre/uso terapêutico , Microambiente Tumoral , Biomimética , Dissulfiram/farmacologia , Ditiocarb/farmacologia , Ditiocarb/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia
3.
J Control Release ; 368: 84-96, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331004

RESUMO

Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc-) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment.


Assuntos
Ferroptose , Glioma , Animais , Camundongos , Biomimética , Cobre , Albuminas , Ditiocarb , Glioma/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
4.
Biol Pharm Bull ; 47(1): 272-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38267041

RESUMO

Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm. The HGNPs were hollow and the surface had protruding structures when prepared using high concentrations of HAuCl4. The simultaneous nucleation of a sacrificial AgCl template and Au nanoparticles may affect the resulting HGNPs. Diethyldithiocarbamate (DDTC) is metabolized from disulfiram and is a repurposed drug currently attracting attention. The chelation of DDTC with copper ion (DDTC-Cu) has been investigated for treating glioma, and here we confirmed the cytotoxic effect of DDTC-Cu towards rat C6 glioma cells in vitro. HGNPs alone were biocompatible and showed little cytotoxicity, whereas a mixture of DDTC-Cu and HGNPs was cytotoxic in a dose dependent manner. The temperature of HGNPs was increased by NIR-laser irradiation. The photothermal effect on HGNPs under NIR-laser irradiation resulted in cytotoxicity towards C6 cells and was dependent on the irradiation time. Photothermal therapy by HGNPs combined and DDTC-Cu was highly effective, suggesting that this combination approach hold promise as a future glioma therapy.


Assuntos
Antineoplásicos , Glioma , Nanopartículas Metálicas , Animais , Ratos , Ditiocarb/farmacologia , Cobre , Ouro , Terapia Fototérmica , Antineoplásicos/farmacologia , Linhagem Celular , Glioma/tratamento farmacológico
5.
Environ Sci Pollut Res Int ; 31(5): 7712-7727, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38170352

RESUMO

The multi-source hazardous waste co-disposal system, a recent innovation in the industry, offers an efficient approach for hazardous waste disposal. The incineration fly ash (HFA) produced by this system exhibits characteristics distinct from those of typical incineration fly ash, necessitating the use of adjusted disposal methods. This study examined the physicochemical properties, heavy metal content, heavy metal leaching concentration, and dioxin content of HFA generated by the new co-disposal system and compared them with those of conventional municipal waste incineration fly ash. This study investigated the solidification and stabilization of HFA disposal using the organic agent sodium diethyl dithiocarbamate combined with cement on a field scale. The findings revealed significant differences in the structure, composition, and dioxin content of HFA and FA; HFA contained substantially lower levels of dioxins than FA did. Concerning the heavy metal content and leaching; HFA exhibited an unusually high concentration of zinc, surpassing the permitted emission limits, making zinc content a critical consideration in HFA disposal. After stabilization and disposal, the heavy metal leaching and dioxin content of HFA can meet landfill disposal emission standards when a 1% concentration of 10% sodium diethyldithiocarbamate (DDTC) and 150% silicate cement were employed. These results offer valuable insights into the disposal of fly ash resulting from incineration of mixed hazardous waste.


Assuntos
Dioxinas , Metais Pesados , Eliminação de Resíduos , Cinza de Carvão/química , Eliminação de Resíduos/métodos , Material Particulado , Resíduos Sólidos/análise , Resíduos Perigosos , Carbono , Incineração , Metais Pesados/análise , Zinco , Ditiocarb
6.
J Exp Clin Cancer Res ; 43(1): 30, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263136

RESUMO

BACKGROUND: MEK inhibitors (MEKi) were shown to be clinically insufficiently effective in patients suffering from BRAF wild-type (BRAF WT) melanoma, even if the MAPK pathway was constitutively activated due to mutations in NRAS or NF-1. Thus, novel combinations are needed to increase the efficacy and duration of response to MEKi in BRAF WT melanoma. Disulfiram and its metabolite diethyldithiocarbamate are known to have antitumor effects related to cellular stress, and induction of endoplasmic reticulum (ER) stress was found to synergize with MEK inhibitors in NRAS-mutated melanoma cells. Therefore, we investigated the combination of both therapeutics to test their effects on BRAF-WT melanoma cells and compared them with monotherapy using the MEKi trametinib. METHODS: The effects of combined therapy with disulfiram or its metabolite diethyldithiocarbamate and the MEKi trametinib were evaluated in a series of BRAF-WT melanoma cell lines by measuring cell viability and apoptosis induction. Cytotoxicity was additionally assessed in 3D spheroids, ex vivo melanoma slice cultures, and in vivo xenograft mouse models. The response of melanoma cells to treatment was studied at the RNA and protein levels to decipher the mode of action. Intracellular and intratumoral copper measurements were performed to investigate the role of copper ions in the antitumor cytotoxicity of disulfiram and its combination with the MEKi. RESULTS: Diethyldithiocarbamate enhanced trametinib-induced cytotoxicity and apoptosis induction in 2D and 3D melanoma culture models. Mechanistically, copper-dependent induction of oxidative stress and ER stress led to Janus kinase (JNK)-mediated apoptosis in melanoma cells. This mechanism was also detectable in patient-derived xenograft melanoma models and resulted in a significantly improved therapeutic effect compared to monotherapy with the MEKi trametinib. CONCLUSIONS: Disulfiram and its metabolite represent an attractive pharmaceutical approach to induce ER stress in melanoma cells that potentiates the antitumor effect of MEK inhibition and may be an interesting candidate for combination therapy of BRAF WT melanoma.


Assuntos
Dissulfiram , Melanoma , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas B-raf , Cobre , Ditiocarb , Modelos Animais de Doenças , Quinases de Proteína Quinase Ativadas por Mitógeno
7.
Int J Pharm ; 652: 123800, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38218507

RESUMO

The ancient anti-alcohol drug disulfiram (DSF) has gained widespread attention for its highly effective anti-tumor effects in cancer treatment. Our previous studies have developed liposome of Cu (DDC)2 to overcome the limitations, like the poor water solubility. However, Cu (DDC)2 liposomes still have shown difficulties in severe hemolytic reactions at high doses and systemic toxicity, which have limited their clinical use. Therefore, this study aims to exploratively investigate the feasibility of using DSF or DDC in combination also can chelate Zn2+ to form zinc diethyldithiocarbamate (Zn (DDC)2). Furthermore, this study prepared stable and homogeneous Zn (DDC)2 liposomes, which were able to be released in the tumor microenvironment (TME). The released Zn (DDC)2 was converted to Cu (DDC)2 with the help of endogenous Cu2+-switch enriched in the TME, which has a higher stability constant compared with Zn (DDC)2. In other words, the Cu2+-switch is activated at the tumor site, completing the conversion of the less cytotoxic Zn (DDC)2 to the more cytotoxic Cu (DDC)2 for effective tumor therapy so that the Zn (DDC)2 liposomes in vivo achieved the comparable therapeutic efficacy and provided a safer alternative to Cu (DDC)2 liposomes in cancer therapy.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Lipossomos/uso terapêutico , Ditiocarb/uso terapêutico , Dissulfiram , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Zinco , Cobre/uso terapêutico , Microambiente Tumoral , Descarboxilases de Aminoácido-L-Aromático/uso terapêutico
8.
J Colloid Interface Sci ; 660: 637-646, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266345

RESUMO

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.


Assuntos
Ditiocarb , Neoplasias , Polifenóis , Humanos , Ditiocarb/farmacologia , Cobre/farmacologia , Dióxido de Silício/farmacologia , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Dissulfiram/farmacologia , Neoplasias/tratamento farmacológico , Microambiente Tumoral
9.
Sci Rep ; 13(1): 19685, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37952035

RESUMO

We report a multi-resonant terahertz (THz) metamaterial perfect absorber (MPA)-based biosensor in the working frequency range of [Formula: see text] for sensing of microorganisms (such as fungi, yeast) and wheat pesticides. Nearly [Formula: see text] absorption is realized at [Formula: see text] and [Formula: see text]. We designed our THz MPA sensor making resonators' gap area compatible with the microorganisms' size. To obtain optimum performance of the MPA, a mapping of amplitudes and shifts in the absorption resonance peaks with different structural parameters of the resonators is carried out. A very high-frequency shift is obtained for microorganisms such as Penicillium chrysogenum (fungi), yeast, and pesticides (Imidacloprid, N, N-Diethyldithiocarbamate sodium salt trihydrate, Daminozide, N, N-Diethyldithiocarbamate sodium salt hydrate, and Dicofol). An equivalent circuit model using Advance Design System (ADS) software is developed. The calculated results through the model show similar trends as obtained in the simulations using CST. Investigations of the effect of incidence angle of THz wave on the absorption spectra of the MPA are also carried out. It is found that incidence angle does not impact the stability of the lower resonance absorption peak (1.79THz). Due to the wide working frequency range, the proposed sensor is extremely suitable for the detection of all range of pesticides because their specific absorption fingerprint lies in the frequency range of 0-3.8THz. We believe that our sensor could be a potential detection tool for detecting pesticide residues in agriculture and food products. The THz MPA-based biosensor is capable of detecting a very small change in the effective dielectric constant of the MPA environment. Therefore, it can also offer huge opportunities in label-free biosensing for future biomedical applications.


Assuntos
Praguicidas , Fermento Seco , Saccharomyces cerevisiae , Ditiocarb , Sódio
10.
J Sep Sci ; 46(19): e2300392, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37515359

RESUMO

Challenges and pitfalls in the application of diethyldithiocarbamate derivatization for LC analysis of cisplatin and oxaliplatin, as well as the suitability of this method for different biological matrices with implications for use in routine practice have been identified. The LC of platinum drugs presents a significant challenge. They are polar compounds with poor retention on reverse phase packings. Cisplatin also exhibits poor absorption in UV and ionization in mass spectrometry. Therefore, we developed and optimized a derivatization approach for the LC analysis of total platinum in plasma, plasma ultrafiltrate, peritoneal fluid, and urine. Derivatization in urine proved to be difficult due to the complexity of the matrix, and extended testing was required. Our results highlight the important issues affecting the efficiency, reliability, and suitability of platinum drug derivatization. Although precolumn derivatization is less selective than its postcolumn counterpart, the application of precolumn derivatization is a simple, rapid, and universal approach for the determination of platinum drugs by HPLC. One of its major advantages is that it allows a more affordable analysis using UV detection without the need for additional high-end instrumentation such as a MS detector.


Assuntos
Cisplatino , Platina , Cromatografia Líquida de Alta Pressão/métodos , Ditiocarb , Reprodutibilidade dos Testes
11.
BMC Health Serv Res ; 23(1): 618, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309002

RESUMO

BACKGROUND: Two publicly available Swedish knowledge support systems, "Pharmaceuticals and Environment" on Janusinfo.se and Fass.se, provide environmental information on pharmaceuticals. Janusinfo is provided by the public healthcare system in Stockholm and Fass is provided by the pharmaceutical industry. The objectives of this study were to investigate the experiences among Swedish Drug and Therapeutics Committees (DTCs) with using the databases, retrieve development proposals for these, and investigate the DTCs' challenges with working with pharmaceuticals in the environment. METHODS: A cross-sectional survey with 21 questions, both closed and open-ended, was distributed electronically in March 2022 to Sweden's 21 DTCs. Descriptive statistics and inductive categorization were used for the analysis. RESULTS: A total of 132 respondents from 18 regions filled out the survey. The average regional response rate was 42%. The DTCs used the knowledge supports to consider environmental aspects of pharmaceuticals in their formularies and in education. Respondents were more familiar with Janusinfo compared to Fass but appreciated the availability of both. The DTCs especially valued the concrete proposals for certain active pharmaceutical ingredients on Janusinfo. Respondents requested that all medicinal products have environmental information on Fass. Challenges included lack of data, lack of transparency from the pharmaceutical industry and difficulties considering the environmental aspect of pharmaceuticals in their healthcare practice. Respondents wanted more knowledge, clear messages, and legislation to support their work to reduce the negative environmental impact of pharmaceuticals. CONCLUSIONS: This study demonstrates that knowledge supports for environmental information on pharmaceuticals are valuable for the DTCs in Sweden, but the respondents experienced challenges in their work in this field. The study can provide insights to those in other countries interested in considering environmental aspects in their formulary decision-making.


Assuntos
Ditiocarb , Comitê de Farmácia e Terapêutica , Humanos , Estudos Transversais , Suécia , Bases de Dados Factuais , Preparações Farmacêuticas
12.
Colloids Surf B Biointerfaces ; 225: 113253, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36934611

RESUMO

Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.


Assuntos
Alcoolismo , Ferroptose , Melanoma , Estruturas Metalorgânicas , Síndrome de Abstinência a Substâncias , Animais , Humanos , Ditiocarb/farmacologia , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/metabolismo , Dissulfiram/farmacologia , Dissulfiram/metabolismo , Melanoma/tratamento farmacológico , Cobre/química , Linhagem Celular Tumoral , Sistema y+ de Transporte de Aminoácidos
13.
Sci Rep ; 13(1): 3529, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864097

RESUMO

Metastatic tumor is initiated by metastatic seeds (cancer stem cells "CSCs") in a controlled redox microenvironment. Hence, an effective therapy that disrupts redox balance with eliminating CSCs is critical. Diethyldithiocarbamate (DE) is potent inhibitor of radical detoxifying enzyme (aldehyde dehydrogenase "ALDH"1A) causing effective eradication of CSCs. This DE effect was augmented and more selective by its nanoformulating with green synthesized copper oxide (Cu4O3) nanoparticles (NPs) and zinc oxide NPs, forming novel nanocomplexes of CD NPs and ZD NPs, respectively. These nanocomplexes exhibited the highest apoptotic, anti-migration, and ALDH1A inhibition potentials in M.D. Anderson-metastatic breast (MDA-MB) 231 cells. Importantly, these nanocomplexes revealed more selective oxidant activity than fluorouracil by elevating reactive oxygen species with depleting glutathione in only tumor tissues (mammary and liver) using mammary tumor liver metastasis animal model. Due to higher tumoral uptake and stronger oxidant activity of CD NPs than ZD NPs, CD NPs had more potential to induce apoptosis, suppress hypoxia-inducing factor gene, and eliminate CD44+CSCs with downregulating their stemness, chemoresistance, and metastatic genes and diminishing hepatic tumor marker (α-fetoprotein). These potentials interpreted the highest tumor size reduction with complete eradicating tumor metastasis to liver in CD NPs. Consequently, CD nanocomplex revealed the highest therapeutic potential representing a safe and promising nanomedicine against the metastatic stage of breast cancer.


Assuntos
Neoplasias Hepáticas , Neoplasias Mamárias Animais , Óxido de Zinco , Animais , Feminino , Humanos , Aldeído Desidrogenase , Ditiocarb/farmacologia , Hipóxia Fetal , Fluoruracila , Oxidantes , Microambiente Tumoral , Óxido de Zinco/farmacologia
14.
J Control Release ; 356: 288-305, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870542

RESUMO

Cancer stem cells (CSCs) have been recognized as the culprit for tumor progression, treatment resistance, metastasis, and recurrence while redox homeostasis represents the Achilles' Heel of CSCs. However, few drugs or formulations that are capable of elevating oxidative stress have achieved clinical success for eliminating CSCs. Here, we report hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@HES NPs), which conspicuously suppress CSCs not only in vitro but also in numerous tumor models in vivo. Furthermore, CuET@HES NPs effectively inhibit CSCs in fresh tumor tissues surgically excised from hepatocellular carcinoma patients. Mechanistically, we uncover that hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals via copper­oxygen coordination interactions, thereby promoting copper-diethyldithiocarbamate colloidal stability, cellular uptake, intracellular reactive oxygen species production, and CSCs apoptosis. As all components are widely used in clinics, CuET@HES NPs represent promising treatments for CSCs-rich solid malignancies and hold great clinical translational potentials. This study has critical implications for design of CSCs targeting nanomedicines.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Ditiocarb/química , Ditiocarb/farmacologia , Ditiocarb/uso terapêutico , Cobre/química , Nanopartículas/química , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Amido/química , Linhagem Celular Tumoral , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/uso terapêutico , Células-Tronco Neoplásicas
15.
Nanomedicine ; 47: 102620, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36265559

RESUMO

Copper diethyldithiocarbamate [Cu(DDC)2] is a promising anticancer agent. However, its poor water solubility is a significant obstacle to clinical application. In previous studies, we developed a stabilized metal ion ligand complex (SMILE) method to prepare Cu(DDC)2 nanoparticle (NP) to address the drug delivery challenge. In the current study, we investigate the use of Cu(DDC)2 NP for treating P-glycoprotein (P-gp) mediated drug-resistant cancers. We tested its anticancer efficacy with extensive in vitro cell-based assays and in vivo xenograft tumor model. We also explored the mechanism of overcoming drug resistance by Cu(DDC)2 NP. Our results indicate that Cu(DDC)2 NP is not a substrate of P-gp and thus can avoid P-gp mediated drug efflux. Further, the Cu(DDC)2 NP does not inhibit the activity or the expression of P-gp.


Assuntos
Ditiocarb , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Cobre/farmacologia , Ditiocarb/farmacologia , Nanopartículas Metálicas , Animais , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Angew Chem Int Ed Engl ; 62(12): e202213922, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36585379

RESUMO

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 Cu2+ 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.


Assuntos
Antineoplásicos , Apoptose , Neoplasias , Humanos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cobre/farmacologia , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Ditiocarb , Neoplasias/tratamento farmacológico
17.
Int J Mol Sci ; 25(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38203213

RESUMO

Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts, although their overgrowth can lead to infection in the urogenital tract and at distal sites. Furthermore, ureaplasmas lack a cell wall and do not synthesize folic acid, which causes all ß-lactam and glycopeptide antibiotics, and sulfonamides and diaminopyrimidines, to be of no value. The antibiotics used in therapy belong to the fluoroquinolone, tetracycline, chloramphenicol and macrolide classes. However, the growing incidence of antibiotic-resistant Ureaplasma spp. in the population becomes a problem. Thus, there is a need to search for new drugs effective against these bacteria. Since 1951, the FDA-approved, well-tolerated, inexpensive, orally administered drug disulfiram (DSF) has been used in the treatment of chronic alcoholism, but recently, its antimicrobial effects have been demonstrated. The main biological metabolite of DSF, i.e., N,N-diethyldithiocarbamate (DDC), is generally believed to be responsible for most of the observed pharmacological effects of DSF. In the presented studies, the effect of DDC at concentrations of 2 µg/mL, 20 µg/mL and 200 µg/mL on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested for the first time. The results indicated that all the used DDC concentrations showed both bacteriostatic and bactericidal activity against both tested strains.


Assuntos
Ureaplasma urealyticum , Ureaplasma , Humanos , Ditiocarb , Antibacterianos/farmacologia , Sulfanilamida
18.
Anal Chem ; 94(47): 16328-16336, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36378246

RESUMO

Application of selenium nanoparticle (SeNP)-based fertilizers results in the release of SeNPs to aquatic systems, where SeNPs may transform into inorganic selenite (Se(IV)) and selenate (Se(VI)) with higher toxicity. However, methods for the speciation analysis of different Se species are lacking, hindering the accurate assessment of the risks of SeNPs. Herein, for the first time, a Triton X-45 (TX-45)-based dual-cloud point extraction (CPE) method was established for the selective determination of SeNPs, Se(IV), and Se(VI) in water. TX-45 can adsorb on the surface of SeNPs and facilitate the extraction of SeNPs into the lower TX-45-rich phase in the first CPE, while Se(VI) and Se(IV) retain in the upper aqueous phase. In the second CPE, Se(IV) can selectively associate with diethyldithiocarbamate and be concentrated in the TX-45-rich phase, whereas Se(VI) remains in the upper phase. Different Se species can be isolated and then quantified by ICP-MS. The presence of coexisting ions and dissolved organic matter (0-30 mg C/L) did not interfere with extraction and separation. The feasibility of the presented method was confirmed by the analysis of natural water samples, with a detection limit of 0.03 µg/L and recoveries in the ranges of 61.1-104, 65.5-113, and 80.3-131% for SeNPs, Se(IV), and Se(VI), respectively. This study aims to provide an effective method to track the fate and transformation of SeNPs in aquatic systems and further contribute to estimating the potential risks of SeNPs to environmental organisms and human bodies.


Assuntos
Nanopartículas , Selênio , Humanos , Selênio/análise , Ditiocarb , Octoxinol , Água
19.
Int J Mol Sci ; 23(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36233178

RESUMO

The co-crystallization of the lead(II) complex [Pb(S2CNEt2)2] with tetraiodoethylene (C2I4) gave the co-crystal, [Pb(S2CNEt2)2]∙½C2I4, whose X-ray structure exhibits only a small change of the crystal parameters than those in the parent [Pb(S2CNEt2)2]. The supramolecular organization of the co-crystal is largely determined by an interplay between Pb⋯S tetrel bonding (TeB) and I⋯S halogen bonding (HaB) with comparable contributions from these non-covalent contacts; the TeBs observed in the parent complex, [Pb(S2CNEt2)2], remain unchanged in the co-crystal. An analysis of the theoretical calculation data, performed for the crystal and cluster models of [Pb(S2CNEt2)2]∙½C2I4, revealed the non-covalent nature of the Pb⋯S TeB (-5.41 and -7.78 kcal/mol) and I⋯S HaB (-7.26 and -11.37 kcal/mol) interactions and indicate that in the co-crystal these non-covalent forces are similar in energy.


Assuntos
Ditiocarb , Halogênios , Halogênios/química , Hidrocarbonetos Iodados , Chumbo , Modelos Moleculares
20.
Antimicrob Agents Chemother ; 66(11): e0083222, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36255253

RESUMO

New anti-Entamoeba histolytica multistage drugs are needed because only one drug class, nitroimidazoles, is available for treating invasive disease, and it does not effectively eradicate the infective cyst stage. Zinc ditiocarb (ZnDTC), a main metabolite of the FDA-approved drug disulfiram, was recently shown to be highly effective against the invasive trophozoite stage. In this brief report, we show that ZnDTC is active against cysts, with similar potency to first-line cysticidal drug paromomycin.


Assuntos
Alcoolismo , Cistos , Entamoeba histolytica , Parasitos , Animais , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Ditiocarb/metabolismo , Ditiocarb/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...