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1.
J Inorg Biochem ; 240: 112091, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36527994

RESUMEN

Gallium and indium octahedral complexes with isoniazid derivative ligands were successfully prepared. The ligands, isonicotinoyl benzoylacetone (H2L1) and 4-chlorobenzoylacetone isonicotinoyl hydrazone (H2L2), and their respective coordination compounds with gallium and indium [GaL1(HL1)] (GaL1), [GaL2(HL2)] (GaL2), [InL1(HL1)] (InL1) and [InL2(HL2)] (InL2) were investigated by NMR, ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction and elemental analysis. In vitro interaction studies with human serum albumin (HSA) evidenced a moderate affinity of all complexes with HSA through spontaneous hydrophobic interactions. The greatest suppression of HSA fluorescence was caused by GaL2 and InL2, which was associated to the higher lipophilicity of H2L2. In vitro interaction studies with CT-DNA indicated weak interactions of the biomolecule with all complexes. Cytotoxicity assays with MCF-7 (breast carcinoma), PC-3 (prostate carcinoma) and RWPE-1 (healthy human prostate epithelial) cell lines showed that complexes with H2L2 are more active and selective against MCF-7, with the greatest cytotoxicity observed for InL2 (IC50 = 10.34 ± 1.69 µM). H2L1 and H2L2 were labelled with gallium-67, and it was verified that 67GaL2 has a greater lipophilicity than 67GaL1, as well as higher stability in human serum or in the presence of apo-transferrin. Cellular uptake assays with 67GaL1 and 67GaL2 evidenced that the H2L2-containing radiocomplex has a higher accumulation in MCF-7 and PC-3 cells than the non-halogenated congener 67GaL1. The anti-Mycobacterium tuberculosis assays revealed that both ligands and metal complexes are potent growth inhibitors, with MIC90 (µg mL-1) values observed from 0.419 ± 0.05 to 1.378 ± 0.21.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Galio , Mycobacterium tuberculosis , Neoplasias , Tuberculosis , Masculino , Humanos , Isoniazida/farmacología , Indio/farmacología , Galio/farmacología , Galio/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Ligandos , Antineoplásicos/farmacología , Antineoplásicos/química
2.
Biol Trace Elem Res ; 201(2): 766-775, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35262856

RESUMEN

BACKGROUND: Aluminum and indium are widely used in industrial manufacturing, in pharmaceutical products, in medical treatments, and in food packaging, so they could reach organisms by different way. In order to clarify whether these elements are dangerous, we already demonstrated the ultrastructural modifications observed in the testicles, the epididymides, and the seminal vesicles of rat. Their pro-oxidative effect was also confirmed concomitantly to a decrease in anti-oxidant defenses in the blood, the testicles, and the liver. Thus, it seemed very logic to evaluate damages in the reproductive organs, especially on the exocrine and endocrine functions of the testicles. METHODS: Aluminum and indium were intraperitoneally administered to male Wistar rats. Sperm solution was obtained from cauda epididymides. Motility, viability, density, and malformation of spermatozoa solution were assessed. Serum total unconjugated testosterone concentrations were measured using RIA technique. RESULTS: Our results showed a decrease in weight of the testicles, epididymides, and seminal vesicles of indium-treated rats and an increase in the weight of their kidneys. A decrease in motility, viability, and density of epididymides stored sperm as well as generation of many spermatozoa malformations was also observed especially in indium-treated rats. Testosterone levels were increased in indium but were enhanced in aluminum group. This confirmed our previous studies showing that aluminum and indium are toxic for the testicular tissues. This could be explained by the generation of reactive oxygen species (ROS) affecting strongly the exocrine and the endocrine functions of the testicles. CONCLUSION: Aluminum and indium are disturbing elements for the exocrine and endocrine functions of rat testicles.


Asunto(s)
Aluminio , Indio , Masculino , Ratas , Animales , Ratas Wistar , Indio/farmacología , Aluminio/toxicidad , Tamaño de los Órganos , Semen , Espermatozoides , Testículo , Testosterona , Motilidad Espermática , Recuento de Espermatozoides
3.
J Med Chem ; 65(7): 5392-5406, 2022 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-35324188

RESUMEN

To effectively integrate diagnosis and therapy for tumors, we proposed to develop an indium (In) agent based on the unique property of human serum albumin (HSA) nanoparticles (NPs). A novel In(III) quinoline-2-formaldehyde thiosemicarbazone compound (C5) was optimized with remarkable cytotoxicity and fluorescence to cancer cells in vitro. An HSA-C5 complex NP delivery system was then successfully constructed. Importantly, the HSA-C5 complex NPs have stronger bioimaging and therapeutic efficiency relative to C5 alone in vivo. Besides, the results of gene chip analysis revealed that C5/HSA-C5 complex NPs act on cancer cells through multiple mechanisms: inducing autophagy, apoptosis, and inhibiting the PI3K-Akt signaling pathway.


Asunto(s)
Indio , Nanopartículas , Línea Celular Tumoral , Humanos , Indio/farmacología , Fosfatidilinositol 3-Quinasas , Albúmina Sérica Humana/metabolismo
4.
J Med Chem ; 64(19): 14587-14602, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34609868

RESUMEN

To overcome the resistance of cancer cells to platinum-based drugs and effectively suppress tumor growth, we developed a novel indium (In) agent based on liposomes (Lips). Thus, we not only obtained an In(III) thiosemicarbazone agent (5b) with remarkable cytotoxicity by optimizing a series of In(III) thiosemicarbazone agents (1b-5b) but also successfully constructed a novel 5b-loaded Lip (5b-Lip) delivery system. Importantly, in vitro and in vivo results revealed that 5b/5b-Lip overcame the tumor cell resistance and effectively inhibited MCF-7/DDP tumor growth. In addition, Lips improved the intracellular accumulation of 5b. We also confirmed the mechanism by which 5b/5b-Lip overcomes breast cancer cell resistance. 5b/5b-Lip cannot act against DNA in cancer cells but attacks the two cell components in the tumor microenvironment, namely, by inducing apoptosis and lethal autophagy of cancer cells and resetting tumor-promoting M2 macrophages to the tumor-killing M1 phenotype.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Indio/farmacología , Liposomas , Microambiente Tumoral , Animales , Neoplasias de la Mama/patología , Femenino , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto
5.
J Mater Chem B ; 9(1): 85-93, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33043953

RESUMEN

Gallium-based liquid metals have increasing applications in a wide variety of emerging areas and they are involved more in frontier studies, the energy industry and additive manufacturing production, and even in daily life. When exposed to open air, large amounts of microorganisms may interact with liquid metals. However, the research of the relationship between pure gallium-based liquid metals and bacterial cells is still limited. In this study, the antibacterial properties of eutectic gallium-indium (EGaIn) alloys were tested against the typical Gram-negative bacteria-Escherichia coli and the Gram-positive bacteria-Staphylococcus aureus and the experimental results displayed that the antibacterial rates reached 100%. We also explored the mechanism of the anti-bacterial properties of EGaIn alloys by measuring the surface composition of the EGaIn film and the concentration of dissolved metal ions. The morphology of the bacterial cells showed that the cell growth and division were influenced by exposure to EGaIn. We also found that the synergistic antibacterial effect came along with the production of reactive oxygen species (ROS). Moreover, the EGaIn film showed enhanced antibacterial activity compared to gallium nitrate at the same initial ion concentration in the solution. This study shows the enormous potential of the anti-bacterial effect of liquid metals.


Asunto(s)
Antibacterianos/metabolismo , Galio/metabolismo , Indio/metabolismo , Líquido Intracelular/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Galio/farmacología , Humanos , Indio/farmacología , Líquido Intracelular/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo
6.
Dalton Trans ; 49(47): 17207-17220, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33201167

RESUMEN

The anticancer function and anticancer mechanism of indium (In) complexes still remain mysterious to date. Furthermore, it is greatly challenging to design a multi-functional metal agent that not only kills cancer cells but also inhibits their invasion and metastasis. Thus, to develop novel next-generation anticancer metal agents, we designed and synthesized a series of novel In(iii) 2,6-diacetylpyridine bis(thiosemicarbazide) complexes (C1-C4) for the first time and then investigated their structure-activity relationships with human urinary bladder cancer (T-24) cells. In particular, C4 not only showed higher cytotoxicity to cancer cells and less toxicity toward normal cells relative to cisplatin but also inhibited cell invasion and metastasis of T-24 cells. Interestingly, C4 acted against T-24 cells exhibiting multiple mechanisms: (1) arresting the S-phase of cell cycle via regulation of cytokine kinases, (2) activating the mitochondrial-mediated apoptosis, endoplasmic reticulum-stress-mediated cell death, PERK and c-Jun N-terminal kinase 1 (JNK) cell signaling pathways, and (3) inhibiting the expression of telomerase via the regulation of c-myc and h-TERT proteins. Our results suggested that C4 may be developed as a potential multi-functional and multi-targeting anticancer candidate.


Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Indio/farmacología , Tiosemicarbazonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indio/química , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Tiosemicarbazonas/química
7.
Sci Rep ; 10(1): 20348, 2020 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-33230153

RESUMEN

The use of microorganisms that allows the recovery of critical high-tech elements such as gallium (Ga) and indium (In) has been considered an excellent eco-strategy. In this perspective, it is relevant to understand the strategies of Ga and In resistant strains to cope with these critical metals. This study aimed to explore the effect of these metals on two Ga/In resistant strains and to scrutinize the biological processes behind the oxidative stress in response to exposure to these critical metals. Two strains of Serratia fonticola, A3242 and B2A1Ga1, with high resistance to Ga and In, were submitted to metal stress and their protein profiles showed an overexpressed Superoxide Dismutase (SOD) in presence of In. Results of inhibitor-protein native gel incubations identified the overexpressed enzyme as a Fe-SOD. Both strains exhibited a huge increase of oxidative stress when exposed to indium, visible by an extreme high amount of reactive oxygen species (ROS) production. The toxicity induced by indium triggered biological mechanisms of stress control namely, the decrease in reduced glutathione/total glutathione levels and an increase in the SOD activity. The effect of gallium in cells was not so boisterous, visible only by the decrease of reduced glutathione levels. Analysis of the cellular metabolic viability revealed that each strain was affected differently by the critical metals, which could be related to the distinct metal uptakes. Strain A3242 accumulated more Ga and In in comparison to strain B2A1Ga1, and showed lower metabolic activity. Understanding the biological response of the two metal resistant strains of S. fonticola to stress induced by Ga and In will tackle the current gap of information related with bacteria-critical metals interactions.


Asunto(s)
Contaminantes Ambientales/farmacología , Galio/farmacología , Indio/farmacología , Serratia/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Electrónica/instrumentación , Contaminantes Ambientales/aislamiento & purificación , Contaminantes Ambientales/metabolismo , Galio/aislamiento & purificación , Galio/metabolismo , Humanos , Indio/aislamiento & purificación , Indio/metabolismo , Pruebas de Sensibilidad Microbiana , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/agonistas , Especies Reactivas de Oxígeno/metabolismo , Serratia/crecimiento & desarrollo , Serratia/metabolismo , Superóxido Dismutasa/química
8.
Sci Rep ; 10(1): 10741, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32612147

RESUMEN

Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis. In this study, we examined 8-nitroG formation in A549 cultured human lung epithelial cells treated with indium compounds, including nanoparticles of indium oxide (In2O3) and indium-tin oxide (ITO), and indium chloride (InCl3). We performed fluorescent immunocytochemistry to examine 8-nitroG formation in indium-exposed A549 cells. All indium compounds significantly increased 8-nitroG formation in A549 cells at 5 ng/ml after 4 h incubation. 8-NitroG formation was largely reduced by 1400 W, methyl-ß-cyclodextrin (MBCD) and monodansylcadaverine (MDC), suggesting the involvement of nitric oxide synthase and endocytosis. 8-NitroG formation in A549 cells was also largely suppressed by small interfering RNA (siRNA) for high-mobility group box-1 (HMGB1), receptor for advanced glycation and end products (AGER, RAGE) and Toll-like receptor 9 (TLR9). These results suggest that indium compounds induce inflammation-mediated DNA damage in lung epithelial cells via the HMGB1-RAGE-TLR9 pathway. This mechanism may contribute to indium-induced genotoxicity in the respiratory system.


Asunto(s)
Daño del ADN , Guanina/análogos & derivados , Indio/farmacología , Neoplasias Pulmonares/patología , Nanopartículas/administración & dosificación , Células A549 , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Guanina/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Indio/administración & dosificación , Indio/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutágenos , Nanopartículas/química , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo
9.
J Colloid Interface Sci ; 565: 35-42, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-31931297

RESUMEN

Nanoscale ternary chalcogenides have attracted increasing research interest due to their merits of tunable properties and diverse applications in energy and biomedical fields. In this article, silver indium sulfide quantum dots supported by glutathione and polyethyleneimine as dual-ligands have been synthesized through an environmentally friendly and reproducible aqueous method. An emission quantum yield up to 37.2% has been achieved by glutathione as co-ligand bearing electron-rich groups, much higher than that of polyethyleneimine coated quantum dots (4.97%). Both spectroscopic and structural characterizations demonstrate that the photoluminescence enhancement is attributed to change of surface properties by glutathione as co-ligand. Dynamic light scattering (DLS) results and thermogravimetric analysis (TGA) reveal that glutathione covers the QDs with a higher density on the nanocrystal surface than other co-ligands. Therefore, it can effectively passivate the surface trap centers, thus decreasing the non-radiative emission. Moreover, the resultant silver indium sulfide quantum dots present surprisingly long lifetime of 3.69 µs, excellent fluorescent stability and low cytotoxicity, which enables them to be ideal candidate for real-time bioimaging.


Asunto(s)
Indio/química , Luminiscencia , Imagen Óptica , Puntos Cuánticos/química , Plata/química , Sulfuros/química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Indio/farmacología , Ligandos , Tamaño de la Partícula , Procesos Fotoquímicos , Plata/farmacología , Relación Estructura-Actividad , Sulfuros/farmacología , Propiedades de Superficie
10.
Nano Lett ; 20(3): 1980-1991, 2020 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-31999467

RESUMEN

Semiconductor quantum dots (QDs) are attractive fluorescent contrast agents for in vivo imaging due to their superior photophysical properties, but traditional QDs comprise toxic materials such as cadmium or lead. Copper indium sulfide (CuInS2, CIS) QDs have been posited as a nontoxic and potentially clinically translatable alternative; however, previous in vivo studies utilized particles with a passivating zinc sulfide (ZnS) shell, limiting direct evidence of the biocompatibility of the underlying CIS. For the first time, we assess the biodistribution and toxicity of unshelled CIS and partially zinc-alloyed CISZ QDs in a murine model. We show that bare CIS QDs breakdown quickly, inducing significant toxicity as seen in organ weight, blood chemistry, and histology. CISZ demonstrates significant, but lower, toxicity compared to bare CIS, while our measurements of core/shell CIS/ZnS are consistent with literature reports of general biocompatibility. In vitro cytotoxicity is dose-dependent on the amount of metal released due to particle degradation, linking degradation to toxicity. These results challenge the assumption that removing heavy metals necessarily reduces toxicity: indeed, we find comparable in vitro cytotoxicity between CIS and CdSe QDs, while CIS caused severe toxicity in vivo compared to CdSe. In addition to highlighting the complexity of nanotoxicity and the differences between the in vitro and in vivo outcomes, these unexpected results serve as a reminder of the importance of assessing the biocompatibility of core QDs absent the protective ZnS shell when making specific claims of compositional biocompatibility.


Asunto(s)
Cobre , Citotoxinas , Indio , Puntos Cuánticos , Sulfuros , Animales , Cobre/química , Cobre/farmacocinética , Cobre/farmacología , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Células Hep G2 , Humanos , Indio/química , Indio/farmacocinética , Indio/farmacología , Ratones , Ratones Endogámicos BALB C , Puntos Cuánticos/química , Puntos Cuánticos/uso terapéutico , Sulfuros/química , Sulfuros/farmacocinética , Sulfuros/farmacología
11.
Int J Nanomedicine ; 14: 9577-9586, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31824152

RESUMEN

PURPOSE: Quantum dots (QDs) are widely used semiconductor nanomaterials. Indium phosphide/zinc sulfide (InP/ZnS) QDs are becoming potential alternatives to toxic heavy metal-containing QDs. However, the potential toxicity and, in particular, the immunotoxicity of InP/ZnS QDs are unknown. This study aimed to investigate the impacts of InP/ZnS QDs on inflammatory responses both in vivo and in vitro. METHODS: Mice and mouse bone marrow-derived macrophages (BMMs) were exposed to polyethylene glycol (PEG) coated InP/ZnS QDs. The infiltration of neutrophils and the release of interleukin-6 (IL-6) were measured using a hematology analyzer and an enzyme-linked immunosorbent assay (ELISA) for the in vivo test. Cytotoxicity, IL-6 secretion, oxidative stress and endoplasmic reticulum (ER) stress were studied in the BMMs, and then, inhibitors of oxidative stress and ER stress were used to explore the mechanism of the InP/ZnS QDs. RESULTS: We found that 20 mg/kg PEG-InP/ZnS QDs increased the number of neutrophils and the levels of IL-6 in both peritoneal lavage fluids and blood, which indicated acute phase inflammation in the mice. PEG-InP/ZnS QDs also activated the BMMs and increased the production of IL-6. In addition, PEG-InP/ZnS QDs triggered oxidative stress and the ER stress-related PERK-ATF4 pathway in the BMMs. Moreover, the inflammatory response caused by the PEG-InP/ZnS QDs could be attenuated in the macrophages by blocking the oxidative stress or the ER stress with inhibitors. CONCLUSION: InP/ZnS QDs can activate macrophages and induce acute phase inflammation both in vivo and in vitro, which may be regulated by oxidative stress and ER stress. Our present work is expected to help clarify the biosafety of InP/ZnS QDs and promote their safe application in biomedical and engineering fields.


Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Indio/farmacología , Macrófagos/patología , Estrés Oxidativo/efectos de los fármacos , Fosfinas/farmacología , Puntos Cuánticos/química , Sulfuros/farmacología , Compuestos de Zinc/farmacología , Animales , Femenino , Depuradores de Radicales Libres/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/genética , Inflamación/patología , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Puntos Cuánticos/ultraestructura , Especies Reactivas de Oxígeno/metabolismo
12.
ACS Appl Mater Interfaces ; 11(39): 35630-35640, 2019 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-31496235

RESUMEN

Many attempts have been made to synthesize cadmium-free quantum dots (QDs), using nontoxic materials, while preserving their unique optical properties. Despite impressive advances, gaps in knowledge of their intracellular fate, persistence, and excretion from the targeted cell or organism still exist, precluding clinical applications. In this study, we used a simple model organism (Hydra vulgaris) presenting a tissue grade of organization to determine the biodistribution of indium phosphide (InP)-based QDs by X-ray fluorescence imaging. By complementing elemental imaging with In L-edge X-ray absorption near edge structure, unique information on in situ chemical speciation was obtained. Unexpectedly, spectral profiles indicated the appearance of In-O species within the first hour post-treatment, suggesting a fast degradation of the InP QD core in vivo, induced mainly by carboxylate groups. Moreover, no significant difference in the behavior of bare core QDs and QDs capped with an inorganic Zn(Se,S) gradient shell was observed. The results paralleled those achieved by treating animals with an equivalent dose of indium salts, confirming the preferred bonding type of In3+ ions in Hydra tissues. In conclusion, by focusing on the chemical identity of indium along a 48 h long journey of QDs in Hydra, we describe a fast degradation process, in the absence of evident toxicity. These data pave the way to new paradigms to be considered in the biocompatibility assessment of QD-based biomedical applications, with greater emphasis on the dynamics of in vivo biotransformations, and suggest strategies to drive the design of future applied materials for nanotechnology-based diagnosis and therapeutics.


Asunto(s)
Hydra/metabolismo , Indio , Fosfinas , Puntos Cuánticos/química , Espectrometría por Rayos X , Animales , Indio/química , Indio/farmacocinética , Indio/farmacología , Fosfinas/química , Fosfinas/farmacocinética , Fosfinas/farmacología
13.
Radiat Res ; 192(4): 422-430, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31390309

RESUMEN

Photodynamic therapy (PDT) uses a combination of photosensitizers with visible light to generate reactive species and selectively kill tumor or unwanted tissue. Znln2S4 nanoparticles are widely implemented in photovoltaic device materials and photolysis water catalysts owing to their unique photoelectric properties. Whether Znln2S4 itself can be used as an effective dye in PDT is still unknown. To determine the effects and potential mechanism of Znln2S4PDT on HepG2 cell apoptosis, electron microscopic analysis was performed to monitor the apoptotic morphology of HepG2 cells upon exposure to Znln2S4-PDT. Flow cytometry was performed to measure the apoptosis rate and intracellular ROS production. Western blot and ELISA were performed to reveal the expression changes in Bax, caspase-3 and caspase-9. Data from this work suggested that cells exhibited the typical apoptotic morphology in response to Znln2S4-PDT, with high apoptotic rate. The intracellular ROS production after Znln2S4-PDT occurred in a dose-dependent manner. Moreover, Znln2S4-PDT augmented the expression levels of pro-apoptosis factors, especially, Bax, caspase-3 and caspase-9. Taken together, our novel findings, Znln2S4-PDT elicited HepG2 cell apoptosis, suggesting Znln2S4 as a promising photosensitizer candidate for cancer therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Indio/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Compuestos de Zinc/farmacología , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Espacio Intracelular/efectos de la radiación , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo
14.
Angew Chem Int Ed Engl ; 58(33): 11414-11418, 2019 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-31184802

RESUMEN

The emergence of multidrug-resistant (MDR) pathogens represents one of the most urgent global public health crises. Light-activated quantum dots (QDs) are alternative antimicrobials, with efficient transport, low cost, and therapeutic efficacy, and they can act as antibiotic potentiators, with a mechanism of action orthogonal to small-molecule drugs. Furthermore, light-activation enhances control over the spatiotemporal release and dose of the therapeutic superoxide radicals from QDs. However, the limited deep-tissue penetration of visible light needed for QD activation, and concern over trace heavy metals, have prevented further translation. Herein, we report two indium phosphide (InP) QDs that operate in the near-infrared and deep-red light window, enabling deeper tissue penetration. These heavy-metal-free QDs eliminate MDR pathogenic bacteria, while remaining non-toxic to host human cells. This work provides a pathway for advancing QD nanotherapeutics to combat MDR superbugs.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Indio/farmacología , Luz , Fosfinas/farmacología , Puntos Cuánticos , Farmacorresistencia Bacteriana Múltiple , Células HeLa , Humanos , Indio/administración & dosificación , Fosfinas/administración & dosificación
15.
J Biol Inorg Chem ; 24(2): 191-210, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30673878

RESUMEN

Zinc(II) (5), indium(III) (6), and lutetium(III) (7) phthalocyanines (Pcs) peripherally substituted with poly (ethylene glycol) (PEG) monomethyl ether 2000 (PEGME-2000) blocks were synthesized via Sonogashira coupling reaction with high yields and their photophysical, photochemical and photobiological properties were investigated. We elucidated the interactions of these compounds with calf thymus DNA and bovine serum albumin (BSA), and determined K(DNA) and K(BSA) binding constants at degrees of 105 and 106, respectively. Singlet oxygen quantum yields were found (Ф∆ = 0.44, 0.54, and 0.68 for 5, 6, and 7, respectively). Thermodynamic parameters, as well as thermal denaturation profile of double-stranded CT-DNA were examined to determine the type of binding mode. According to our experimental data, we report that PEGME-2000 favors the formation of binary complex between DNA, and phthalocyanine complexes. Therein, thermodynamic data suggest that this binding mode is indeed spontaneous under reported conditions, and rather non-specific. Additionally, Pcs 5, 6, and 7 substituted with PEGME-2000 blocks showed antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi (yeast), and Pc 5 had the highest antimicrobial activity among them, as revealed by disc diffusion assay results. In short, our results suggest that these compounds could be used for photodynamic therapy, they have both antibacterial and antifungal activity, and the binding ability of new phthalocyanines 5, 6, and 7 with BSA paves the way for their utilization as drug vehicle in blood plasma.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Fármacos Fotosensibilizantes/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Bovinos , ADN/química , Éteres/química , Éteres/farmacología , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Indio/química , Indio/farmacología , Indoles/química , Indoles/farmacología , Isoindoles , Lutecio/química , Lutecio/farmacología , Pruebas de Sensibilidad Microbiana , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Procesos Fotoquímicos , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Polietilenglicoles/química , Polietilenglicoles/farmacología , Albúmina Sérica Bovina/química , Compuestos de Zinc
16.
Photodiagnosis Photodyn Ther ; 25: 325-333, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30658105

RESUMEN

This work reports on the linkage of 2(3),9(10),16(17),23(24) tetrakis [(benzo[d]thiazol-2-yl phenoxy) phthalocyaninato] zinc(II) (1) and indium(III) chloride (2) to gold speckled silica (GSS) nanoparticles via gold to sulphur (Au-S) and gold to nitrogen (Au-N) self-assembly to form the conjugates: 1-GSS and 2-GSS. The formed conjugates were characterized using microscopic and spectroscopic techniques, and the photophysicochemical properties and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) were studied. The conjugates afforded decrease in fluorescence quantum yields with corresponding increase in triplet and singlet oxygen quantum yields when compared to phthalocyanines alone. Singlet oxygen is cytotoxic to cancer cells hence it is important for PDT. The in vitro dark toxicity of complex 2 and 2-GSS against MCF-7 cells showed ≥93% viable cells within concentration ranges of 10-160 µg/mL. 2-GSS showed enhanced PDT activity with less than 50% viable cells at 80 µg/mL as compared to 2 and GSS alone which showed >60% viable cells within 10-160 µg/mL. The observed improvements in the PDT activity of 2-GSS could be attributed to the high singlet oxygen generation of 2-GSS compared to 2 alone in addition to the phototoxicity of GSS.


Asunto(s)
Indoles/farmacología , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete/metabolismo , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/química , Oro/química , Humanos , Indio/farmacología , Isoindoles , Células MCF-7 , Fármacos Fotosensibilizantes/administración & dosificación , Dióxido de Silicio/química , Zinc/farmacología
17.
J Colloid Interface Sci ; 533: 358-368, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30172146

RESUMEN

The problem of marine life attachment and its pollution to facilities has caused a lot of great troubles in the development and application of marine resources. The holes generated by the photocatalytic coating materials under sunlight may produce strong oxidizing species and showed a significant effect on the degradation and bactericidal performance of environmental organic matter. In this paper, a novel bismuth vanadate/indium vanadate (BiVO4/InVO4) composite with cherimoya-like microstructure was fabricated using new vanadium source. It is found that the composite materials showed enhanced photocatalytic antifouling property. The degradation efficiency of the model pollutes (Rhodamine B, RhB) achieved 99.775% within 280 min over BiVO4/InVO4 nanostructures, and the sterilization rate of E. coli, S. aureus, P. aeruginosa and A. carterae achieved 99.7148%, 99.5519%, 99.5411% and 96.00%, respectively. Moreover, the circulate photocatalytic degradation of antibacteria experiments demonstrated the outstanding stability and reusability of BiVO4/InVO4 composite. According to the active free radical trapping experiments, the hydroxyl radical (OH) and superoxide radical (O2-) were certified to be the main reactive oxygen species in the BiVO4/InVO4 system. The distinctly enhanced photocatalytic performance of BiVO4/InVO4 nanomaterial primarily resulted from the narrow bandgap (about 1.86 eV). This study not only provides a new method for developing novel antibacterial materials, but also introduces a visible light-driven photocatalyst for water treatment and marine antifouling, especially for red tide control.


Asunto(s)
Antibacterianos/farmacología , Incrustaciones Biológicas/prevención & control , Bismuto/farmacología , Indio/farmacología , Vanadatos/farmacología , Antibacterianos/química , Bismuto/química , Catálisis , Dinoflagelados/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Indio/química , Pruebas de Sensibilidad Microbiana , Nanoestructuras/química , Tamaño de la Partícula , Procesos Fotoquímicos , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Vanadatos/química
18.
Chemistry ; 24(71): 19060-19065, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30281860

RESUMEN

Two-dimensional (2D) nanoflakes represent an appealing class of materials for optoelectronics applications due to their unique layered structures and excellent electronic properties. However, the lack of easy-to-manipulate and effective methods for large-scale production of these 2D materials limits their potential for applications. Also, few efforts have been made to explore their applications in biological fields. This work reports the preparation of large quantities of 2D In2 Se3 nanosheets through a solvent exfoliation technique. Transmission electron microscopy and atomic force microscopy results show that the In2 Se3 nanosheets are obtained with lateral sizes of tens of nanometers to hundreds of nanometers and thickness of 2-17 layers. Raman features coupled with the X-ray diffractometry results unequivocally confirm the as-prepared In2 Se3 nanosheets to be α phase. Moreover, these α-In2 Se3 nanosheets exhibit an excellent near-infrared (NIR) photothermal performance under an 808 nm laser irradiation. NIR photo-excitation of the α-In2 Se3 nanosheets in the presence of bacteria leads to a significant antibacterial effect, suggesting that these nanosheets have great potential to be photothermal antibacterial agents. Our work on α-In2 Se3 nanosheets presents an available method for exfoliating 2D layered materials, and highlights the potential application in chemical and biological fields of α-In2 Se3 nanosheets.


Asunto(s)
Antibacterianos/química , Infecciones Bacterianas/prevención & control , Indio/química , Nanoestructuras/química , Selenio/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/efectos de la radiación , Humanos , Hipertermia Inducida/métodos , Indio/farmacología , Rayos Infrarrojos , Modelos Moleculares , Nanoestructuras/ultraestructura , Fototerapia/métodos , Selenio/farmacología , Microbiología del Agua
19.
J Drug Target ; 26(3): 267-277, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28795849

RESUMEN

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2 mg/mL of QDs) after 24 h indicated low toxicity for the bare QDs and functionalised QDs (about 80-90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.


Asunto(s)
Doxorrubicina/química , Ácido Fólico/química , Glucosamina/química , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Puntos Cuánticos/química , Células A549 , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Femenino , Citometría de Flujo , Ácido Fólico/administración & dosificación , Glucosamina/administración & dosificación , Humanos , Indio/química , Indio/farmacología , Fosfinas/química , Fosfinas/farmacología , Puntos Cuánticos/administración & dosificación , Sulfuros/química , Sulfuros/farmacología , Compuestos de Zinc/química , Compuestos de Zinc/farmacología
20.
J Biomed Mater Res B Appl Biomater ; 106(5): 1686-1697, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-28842963

RESUMEN

Small indium (In) additions up to 5 wt % to the beta-type Ti-40Nb alloy effectively improve its mechanical biofunctionality. The impact on its biocompatibility is addressed in this work. Comparative electrochemical polarization studies and inductively coupled plasma optical emission spectrometry analyses were conducted in Tris-buffered saline (on the basis of 150 mM NaCl) with pH 7.6 and 2.0 at 310 ± 1 K with Ti-6Al-4V as reference. The metal ion releases from beta-type alloys were generally very low, for example, those of In3+ ions from (Ti-40Nb)-4In specimens were below 6 × 10-7 mmol/cm2 . X-ray photoelectron spectroscopy revealed the passivation mainly by Ti- and Nb-oxides with traces of In-oxides as the dominating surface process. In vitro studies demonstrate a better human bone marrow stromal cells (hBMSC) activity on the beta-type alloys in comparison to CP-Ti (grade 2), which is mainly due to their high Nb content. At 24 h after seeding on (Ti-40Nb)-4In the metabolic activity of hBMSC was 1.5-fold higher and after 11 days, the tissue non-specific alkaline phosphatase activity was 1.8-fold higher relative to values for CP-Ti. Surface treatments, like chemical etching or plasma oxidation, change the surface topography and the thickness and composition of the oxide layers, but they are not effective in further improving the cell response. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1686-1697, 2018.


Asunto(s)
Aleaciones , Materiales Biocompatibles , Indio , Leucocitos Mononucleares/metabolismo , Ensayo de Materiales , Aleaciones/química , Aleaciones/farmacocinética , Aleaciones/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Materiales Biocompatibles/farmacología , Humanos , Indio/química , Indio/farmacocinética , Indio/farmacología , Leucocitos Mononucleares/citología , Propiedades de Superficie
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