RESUMEN
A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808â nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808â nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Rayos Infrarrojos , Fotones , Tiofenos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Tiofenos/química , Tiofenos/farmacología , Ratones , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Rutenio/química , Rutenio/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Terapia Fototérmica , Iridio/química , Estructura Molecular , Apoptosis/efectos de los fármacosRESUMEN
Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Iridio/farmacología , Iridio/químicaRESUMEN
A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.
Asunto(s)
Melanoma , Fotoquimioterapia , Humanos , Iridio/farmacología , Iridio/química , Terapia Fototérmica , Luz , Fototerapia , Fármacos Fotosensibilizantes/química , Melanoma/tratamiento farmacológico , Rayos Láser , Línea Celular TumoralRESUMEN
In this paper, Ni/ß-Mo2C(S) and Ni/ß-Mo2C(G) were prepared from solution-derived precursor with two different carbon sources (starch and glucose) and tested as anodic noble-metal-free catalysts in air-cathode microbial fuel cells (MFCs). The carburized catalyst samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the electrocatalyst towards the oxidation of several common microbial fermentation products (formate, lactate, and ethanol) was studied for MFC based on Klebsiella pneumoniae conditions. The composite MFC anodes were fabricated, and their catalytic behavior was investigated. With different carbon sources, the crystalline structure does not change and the crystallinity and surface area increase. The electrocatalytic experiments show that the Ni/ß-Mo2C(G) gives the better bio- and electrocatalytic performance than Ni/ß-Mo2C(S) due to its higher crystallinity and BET surface area.
Asunto(s)
Fuentes de Energía Bioeléctrica , Glucosa/química , Klebsiella pneumoniae/química , Molibdeno/química , Níquel/química , Almidón/química , Biocatálisis , Electrodos , Etanol/química , Formiatos/química , Ácido Láctico/química , Oxidación-ReducciónRESUMEN
Ni3Mo3C was prepared by a modified organic colloid method and explored as anode catalyst for high-performance microbial fuel cell (MFC) based on Klebsiella pneumoniae (K. pneumoniae). The prepared sample was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the sample as anode catalyst for MFC based on K. pneumoniae was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and polarization curve measurement. The results show that the adding of nickel in Mo2C increases the BET surface area of Mo2C and improves the electrocatalytic activity of Mo2C towards the oxidation of microbial fermentation products. The power density of MFC with 3 mg cm(-2) Ni3Mo3C anode is far higher than that of the MFC with carbon felt as anode without any catalyst, which is 19 % higher than that of Mo2C anode and produced 62 % as much as that of Pt anode, indicating that Ni3Mo3C is comparative to noble metal platinum as anode electrocatalyst for MFCs by increasing the loading.
Asunto(s)
Fuentes de Energía Bioeléctrica/microbiología , Carbono/química , Electrodos/microbiología , Klebsiella pneumoniae/química , Molibdeno/química , Níquel/química , Catálisis , Espectroscopía Dieléctrica , Klebsiella pneumoniae/metabolismoRESUMEN
BACKGROUND: Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals are essential for screening and diagnosing thyroid dysfunction during pregnancy. The aim of this study was to establish method- and trimester-specific TSH and FT4 reference intervals in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600. METHODS: A cross-sectional dataset analysis was performed. A total of 3507 participants were recruited, and 2743 were eligible for analysis to set reference intervals. TSH, FT4, and thyroid peroxidase antibody (TPOAb) levels were analyzed with the Beckman Coulter UniCel™ DxI 600 Access® immunoassay system. Ranges between the 2.5th and 97.5th percentiles were defined as reference intervals for TSH and FT4. RESULTS: The calculated reference intervals for the first, second, and third trimesters were TSH: 0.06-3.13, 0.07-4.13 and 0.15-5.02 mIU/L, respectively, and FT4: 8.72-15.22, 7.10-13.55 and 6.16-12.03 pmol/L, respectively. CONCLUSIONS: Our reference intervals for TSH and FT4 are distinct from the ranges reported in the DxI 600 instruction manual and previously reported data, confirming the importance of method-specific reference intervals.