RESUMEN

Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.

Asunto(s)

Radioisótopos de Yodo , Compuestos de Manganeso , Óxido Nítrico , Óxidos , Especies Reactivas de Oxígeno , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Humanos , Animales , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Óxidos/química , Óxidos/farmacología , Radioisótopos de Yodo/química , Apoptosis/efectos de los fármacos , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ratones , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Ratones Endogámicos BALB C , Terapia por Ultrasonido , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ondas Ultrasónicas , Línea Celular Tumoral

RESUMEN

Background: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME). Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH-responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect. Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy. Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.

Asunto(s)

Carbonato de Calcio , Calcio , Nanopartículas , Microambiente Tumoral , Humanos , Animales , Nanopartículas/química , Calcio/química , Carbonato de Calcio/química , Carbonato de Calcio/farmacología , Microambiente Tumoral/efectos de los fármacos , Células HeLa , Especies Reactivas de Oxígeno/metabolismo , Ratones , Ácido Hialurónico/química , Porfirinas/química , Porfirinas/farmacología , Porfirinas/farmacocinética , Porfirinas/administración & dosificación , Terapia Fototérmica/métodos , Concentración de Iones de Hidrógeno , Terapia por Ultrasonido/métodos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas Capa por Capa

RESUMEN

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a promising treatment approach for multidrug resistant infections. PDT/PTT combination therapy can more efficiently eliminate pathogens without drug resistance. The key to improve the efficacy of photochemotherapy is the utilization efficiency of non-radiation energy of phototherapy agents. Herein, a facile phototherapy molecule (SCy-Le) with the enhancement of non-radiative energy transfer is designed by an acid stimulation under a single laser. Introduction of the protonated receptor into SCy-Le results in a distorted intramolecular charge in the infected acidic microenvironment, pH ≈ 5.5, which in turn, enhances light capture, reduces the singlet-triplet transition energies (ΔES1-T1), promotes electron system crossing, enhances capacity of reactive oxygen species generation, and causes a significant increase in temperature by improving vibrational relaxation. SCy-Le shows more than 99% bacterial killing rate against both methicillin-resistant Staphylococcus aureus and its biofilms in vitro and causes bacteria-induced wound healing in mice. This work will provide a new perspective for the design of phototherapy agents, and the emerging photochemotherapy will be a promising approach to combat the problem of antibiotic resistance.

Asunto(s)

Biopelículas , Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Ratones , Biopelículas/efectos de los fármacos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Fototerapia/métodos , Antibacterianos/farmacología , Antibacterianos/química , Ratones Endogámicos BALB C , Cicatrización de Heridas/efectos de los fármacos

RESUMEN

Sonodynamic therapy (SDT), a tumor treatment modality with high tissue penetration and low side effects, is able to selectively kill tumor cells by producing cytotoxic reactive oxygen species (ROS) with ultrasound-triggered sonosensitizers. N-type inorganic semiconductor TiO2 has low ROS quantum yields under ultrasound irradiation and inadequate anti-tumor activity. Herein, by using atomic layer deposition (ALD) to create a heterojunction between porous TiO2 and CoOx, the sonodynamic therapy efficiency of TiO2 can be improved. Compared to conventional techniques, the high controllability of ALD allows for the delicate loading of CoOx nanoparticles into TiO2 pores, resulting in the precise tuning of the interfaces and energy band structures and ultimately optimal SDT properties. In addition, CoOx exhibits a cascade of H2O2→O2→·O2 - in response to the tumor microenvironment, which not only mitigates hypoxia during the SDT process, but also contributes to the effect of chemodynamic therapy (CDT). Correspondingly, the synergistic CDT/SDT treatment is successful in inhibiting tumor growth. Thus, ALD provides new avenues for catalytic tumor therapy and other pharmaceutical applications.

Asunto(s)

Peróxido de Hidrógeno , Nanopartículas , Humanos , Especies Reactivas de Oxígeno , Catálisis , Hipoxia

RESUMEN

Mitochondrial viscosity is a critical factor affecting numerous physiological processes, including phagocytosis. Abnormal viscosity in mitochondria is related to some pathological activities and diseases. Evaluating and detecting the changes in mitochondrial viscosity in vivo is crucial. Thus, a mitochondria-targeted red-emitting fluorescent probe (VP) was prepared, and can be used to detect viscosity with high selectivity and sensitivity. The synthesis of probe VP was as simple as two steps and the cost was low. In addition, the fluorescence intensity (log I615) exhibited an excellent relationship with viscosity (log η) in the range of 0.5 - 2.5 (R2 = 0.9985) in water/glycerol mixture. It is noteworthy that the probe VP displayed the highest signal-to-noise ratio (about 50-fold) for viscosity in water and glycerol system. The probe VP can visualize the mitochondrial viscosity change in living cells. More importantly, phagocytic test for BV2 cells further demonstrated that phagocytosis decreased with increased viscosity. Furthermore, VP was successfully used for monitoring the mitophagy process induced by starvation, and mitochondrial viscosity exhibited enhancement during mitophagy. The probe was a potential tool for studying viscosity and phagocytosis.

Asunto(s)

Glicerol , Imagen Óptica , Humanos , Viscosidad , Células HeLa , Imagen Óptica/métodos , Mitocondrias/patología , Colorantes Fluorescentes , Agua

RESUMEN

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with ineffective treatment and poor prognosis. It is in great demand to develop a novel theranostic strategy for accurate diagnosis and targeted treatment of TNBC. In the present study, one nanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guided chemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapy capacity toward TNBC, was innovatively constructed. The nanoplatform was prepared by covalently conjugating ICG-decorated hyaluronic acid (HA) on Fe3+-chelated polydopamine (PDA). HA facilitated the targeting and accumulating of the nanoplatform in tumor tissue and cells of TNBC, thus producing enhanced magnetic resonance signal. Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzed cleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared (NIR) fluorescence signal, allowing for the activatable NIR fluorescence imaging. On the other hand, Fe3+ in the nanoplatform could be reduced to reactive Fe2+ in tumor microenvironment, guaranteeing efficient Fenton reaction-mediated CDT. The combination of ICG with Fe-PDA enhanced the NIR absorption of the nanoplatform so that considerable PTT/PDT and photothermal imaging were achieved under 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatform integrates the potential of TNBC-targeting, precise NIR fluorescence/magnetic resonance/photothermal trimodal imaging, efficient treatment via synergistic CDT/PDT/PTT, as well as excellent biocompatibility. Therefore, this multifunctional nanoplatform provides a simple and versatile strategy for imaging-guided theranostics of TNBC.

Asunto(s)

Nanopartículas , Fotoquimioterapia , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Terapia Fototérmica , Línea Celular Tumoral , Fototerapia , Fotoquimioterapia/métodos , Nanomedicina Teranóstica , Microambiente Tumoral

RESUMEN

Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics.

RESUMEN

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo, especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

Asunto(s)

Neoplasias Esofágicas , Nanopartículas , Fotoquimioterapia , Porfirinas , Línea Celular Tumoral , Factor de Crecimiento Epidérmico , Neoplasias Esofágicas/tratamiento farmacológico , Glutatión/farmacología , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Medicina de Precisión , Nanomedicina Teranóstica/métodos , Microambiente Tumoral

RESUMEN

Sulfur dioxide (SO2) is a key molecule in organisms that is involved in the regulation of different physiological procedures. Aberrant SO2 causes a variety of diseases, such as cancer and neurodegeneration. Thus, sensitive and selective detection of SO2 is of great importance. Based on the Förster resonance energy transfer (FRET) between green fluorescence carbon dots (GCDs) donor and amide-linked near-infrared fluorescence emissive organic small molecular dye (CDDBT) acceptor, one ratiometric fluorescent nano platform, Mito-GCDs-CDDBT for mitochondria SO2 sensing was constructed. In this FRET sensing system, CDDBT served as the receptor for SO2, and the presence of SO2 enhanced GCDs green fluorescence signal and quenched CDDBT near-infrared fluorescence signal due to the disruption of FRET. Mito-GCDs-CDDBT could sensitively detect SO2 with a detection limit of as low as 0.701 µM. Meanwhile, Mito-GCDs-CDDBT achieved fluorescence imaging to measure the response of cellular exogenous and endogenous SO2 with remarkable mitochondrial targeting. Moreover, Mito-GCDs-CDDBT also realized SO2 sensing in vivo including zebrafish and mice. The as-prepared versatile nanoplatform displayed several advantages, such as mitochondria targeting, FRET-based sensitive detection, and sensing capabilities in biological milieu. Potentially, it could be applied in the diagnostics of SO2 involved diseases.

Asunto(s)

Transferencia Resonante de Energía de Fluorescencia , Dióxido de Azufre , Animales , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes , Células HeLa , Humanos , Ratones , Mitocondrias , Pez Cebra

RESUMEN

Recently, molecules with aggregation-induced luminescence (AIE) characteristics have received more and more attention due to the fluorescence of traditional dyes being easily quenched in the aggregated state. AIE molecules have significant advantages, such as excellent light stability, bright fluorescence, high contrast, and large Stokes shift. These characteristics have aroused wide interest of researchers and opened up new applications in many fields, especially in the field of biological applications. However, AIE molecules or their aggregates have certain limitations in multifunctional biological research due to their low specific targeting ability, poor biocompatibility, and poor stability in physiological body fluids. In order to overcome these problems, a novel nanoparticle, FFM1, was fabricated and characterized. FFM1 displayed good water solubility, biocompatibility, and AIE emission properties. It could target HeLa cells specifically by recognizing their folate receptor. Reactive oxygen triggered by light irradiation induced tumor cell apoptosis. Summarily, FFM1 displayed excellent capacity in target imaging and photodynamic killing of HeLa cells. It has shown potential application value in targeted diagnosis and photodynamic therapy of tumors, and has important guiding significance for the treatment of malignant tumors. It paves a way for the development of a novel strategy for tumor theranostics.

RESUMEN

The hypoxia-activated and nitroreductase-responsive phototheranostic probe has been developed by incorporating a nitro group into a hemicyanine fluorophore. The probe displays extremely sensitive and selective near-infrared fluorescence enhancement to nitroreductase with the detection limit of 2.10 ng/mL. The detection mechanism relies on the nitroreductase-catalyzed reduction of the nitro group to an amino group, along with the generation of the fluorophore. The availability of the probe in fluorescence imaging and photodynamic therapy was demonstrated at cellular level and in vivo. The probe can image endogenous nitroreductase and the hypoxia status of living cells. The probe also exhibits significant phototoxicity to hypoxia tumor cells under the 660 nm laser irradiation. More importantly, the probe has been successfully utilized in imaging tiny tumor (about 6 mm3) and tumor photodynamic therapy in vivo. The proposed probe integrates accurate near-infrared fluorescence imaging and photodynamic therapy into the same molecule, which probably become a promising agent in the early diagnosis and therapy of tumors.

Asunto(s)

Fotoquimioterapia , Colorantes Fluorescentes , Microscopía Fluorescente , Nitrorreductasas , Imagen Óptica

RESUMEN

Pseudomonas aeruginosa (P. aeruginosa) is a popular hospital pathogen and the major cause of morbidity and mortality in patients with cystic fibrosis (CF) and impaired immune system. Herein, we designed and synthesized a series of organic molecules MTEBT-n (n = 1, 2, 3) to specifically and effectively kill P. aeruginosa. Hydrophobic triphenylamine was selected as the skeleton, and hydrophilic primary ammonium salts that can easily penetrate the cell walls of Gram-negative bacteria and accumulate in the bacteria were used to adjust the hydrophilic-hydrophobic ratio of the molecules, resulting in different antibacterial activity. As the hydrophilic-hydrophobic ratio increased in the structures from MTEBT-1 to MTEBT-3, the antibacterial activity of the three molecules were gradually enhanced with killing effects of 25%, 75% and 95% against P. aeruginosa, respectively. The antibacterial mechanisms of MTEBT-n were demonstrated to destroy the bacterial membrane, which could effectively prevent the development of drug resistance. In addition, MTEBT-3 with the highest antibacterial activity could inhibit P. aeruginosa biofilm very well, and heal the P. aeruginosa infected scald wounds. This work provides a potential organic antimicrobial material for clinical antimicrobial therapy of P. aeruginosa infection, and offers a molecular engineering strategy for designing new antimicrobials.

Asunto(s)

Antiinfecciosos , Pseudomonas aeruginosa , Antibacterianos/farmacología , Biopelículas , Humanos , Pruebas de Sensibilidad Microbiana , Cicatrización de Heridas

RESUMEN

The first ultrafast fluorescence probe with response time in seconds (10 s) for fluoride ions (F-) has been proposed by conjugating dimethylthiophosphoryl group as a recognition unit with the near-infrared fluorophore of hemicyanine. The response mechanism is the F--induced cleavage of the dimethylthiophosphoryl group, along with the liberation of the fluorophore, which results in a distinctly enhanced fluorescence intensity at 730 nm (λex = 680 nm). The fluorescence enhancement of the probe is directly proportional to the F- concentration in the range of 10-300 µM with the detection limit of 4.28 µM. The probe has been successfully used to determine F- concentration in real water and toothpaste samples as well as image F- in living cells. The simplicity and quick response of this probe endow it with the ability of detecting F- rapidly in real samples.

Asunto(s)

Colorantes Fluorescentes , Fluoruros , Fluorescencia , Flúor , Agua

RESUMEN

A transferrin receptor (TfR)-targeted nanodrug [green fluorescence emission carbon dot (GCD)-polyethylene glycol (PEG)-transferrin (Tf)@doxorubicin (Dox)] for cancer therapy was developed by functionalizing GCDs with PEG, Tf, and Dox. GCDs were synthesized by the one-step hydrothermal method, followed by conjugating PEG and Tf by covalent bonds and loading Dox by electrostatic interactions. The nanodrug exhibits high stability under neutral conditions and effectively releases Dox at pH of 5.5. GCD-PEG-Tf@Dox can be selectively internalized by TfR-overexpressed tumor cells (MCF-7 and K150) via receptor-mediated endocytosis and further release Dox to the nuclei. As a result, GCD-PEG-Tf@Dox exhibits significant lethality to tumor cells (MCF-7 and K150) but greatly reduced toxicity to normal cells [Chinese hamster ovary cell line (CHO)] compared with free Dox. In vivo studies have confirmed that GCD-PEG-Tf@Dox can effectively inhibit tumor proliferation with negligible side effects.

Asunto(s)

Neoplasias , Transferrina , Animales , Células CHO , Carbono/metabolismo , Línea Celular Tumoral , Cricetinae , Cricetulus , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química , Transferrina/química

RESUMEN

Herein, nitrogen-doped carbon dots (N-CDs) emitting blue fluorescence were prepared using L-tartaric acid and triethylenetetramine through a simple and quick microwave-assisted method. The synthesized N-CDs displayed excitation-dependent fluorescence behavior, and their maximum excitation and emission wavelengths were 350 and 425 nm, respectively. The obtained N-CDs, which featured excellent fluorescence properties with a high fluorescence quantum yield of 31%, were applied to detect metronidazole (MNZ), which can effectively quench the fluorescence intensity of N-CDs due to the inner filter effect. This phenomenon was used as basis to develop a label-free fluorescent method for rapid MNZ determination, with the limit of detection of 0.22 µM and corresponding linear range of 0.5-22 µM. Hence, we had established a fluorescence method for MNZ detection and applied it to detect MNZ in real samples with satisfactory results. Finally, N-CDs with superior biocompatibility were applied for cell imaging and MNZ detection by the changes in fluorescence intensity.

Asunto(s)

Carbono/química , Metronidazol/análisis , Nitrógeno/química , Imagen Óptica , Puntos Cuánticos/química , Animales , Muerte Celular , Supervivencia Celular , Humanos , Células MCF-7 , Leche/química , Espectroscopía de Fotoelectrones , Puntos Cuánticos/ultraestructura , Espectrometría de Fluorescencia

RESUMEN

A highly sensitive and selective fluorescent probe for fluoride ions has been developed by incorporating the dimethylphosphinothionyl group as a recognition moiety into the fluorophore of coumarin. The detection mechanism is based on the fluoride ion-triggered cleavage of the dimethylphosphinothionyl group, followed by the release of coumarin, which leads to a large fluorescence enhancement at 455 nm (λ ex = 385 nm). Under the optimized conditions, the fluorescence enhancement of the probe is directly proportional to the concentration of fluoride ions in the range of 0-30 µM with a detection limit of 0.29 µM, which is much lower than the maximum content of fluoride ions guided by WHO. Notably, satisfying results have been obtained by utilizing the probe to determine fluoride ions in real-water samples and commercially available toothpaste samples. The proposed probe is rather simple and may be useful in the detection of fluoride ions in more real samples.

RESUMEN

Liposomes are a common delivery vehicle for drugs or biologicals, but some common surfactants used as liposome components may cause denaturation and malfunction of serum proteins and cell surface proteins. In this study, we examined the effects of liposome lipid didodecyldimethylammonium bromide (DDAB), nonionic polyoxyethylene sorbitan monooleate 80 (Tween 80), and the equimolar mixture on the properties of serum proteins. Bovine serum albumin was selected as the main model protein, and the effects of the DDAB, Tween 80, and a 1:1 mixture on its spectroscopic behavior were investigated. The effects of surfactants on the five major serum proteins: human serum albumin, apolipoprotein A1, transferrin, fibrinogen and immunoglobulin G were also examined. Finally, the results were verified on human serum. The results indicated that weak interactions exist between human serum proteins and the equimolar mixture of DDAB-Tween 80, significantly different from the strong interactions of DDAB and Tween 80 with proteins. The salient features of cationic-nonionic surfactants enable their use in liposome composition, with improved drug delivery efficiency.

Asunto(s)

Proteínas Sanguíneas/química , Hexosas/química , Compuestos de Amonio Cuaternario/química , Tensoactivos/química , Animales , Bovinos , Dicroismo Circular , Humanos , Liposomas/química , Albúmina Sérica Bovina/química , Espectrometría de Fluorescencia

RESUMEN

Most carbon dots (CDs) conventional fabrication approaches produce single colored fluorescent materials, different methods are required to synthesize distinct carbon dots for specific optical applications. Herein, using one-pot hydrothermal treatment of Syringa obtata Lindl, a facile, low-cost and green assay is achieved in the controllable synthesis of blue and green fluorescent carbon dots. The fluorescent emission of CDs can be well-tuned by adding sodium hydroxide in the precursor solution. Blue fluorescent CDs are applied to Fe3+ sensing with a low detection limit of 0.11 µM of linear range from 0.5 to 80 µM, and then further extended to analysis river water samples. Green fluorescent CDs can be applied to pH detection, which show a remarkable linear enhancement in the green fluorescence emission region when the pH is increased from 1.98 to 8.95. Eventually, the detection of Fe3+ and pH are applied for the living cells fluorescent images in MCF-7 cells are achieved successfully, indicating as-synthesized CDs potential toward diverse application as promising candidate.

Asunto(s)

Técnicas Biosensibles/métodos , Carbono/química , Células/metabolismo , Tecnología Química Verde/métodos , Imagenología Tridimensional , Puntos Cuánticos/química , Muerte Celular , Fluorescencia , Humanos , Concentración de Iones de Hidrógeno , Iones , Límite de Detección , Células MCF-7 , Puntos Cuánticos/ultraestructura , Ríos/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Agua/química

RESUMEN

Cadmium (Cd), a toxic heavy metal, is known to induce renal toxicity by primarily targeting at renal proximal tubule. Endoplasmic reticulum (ER) stress and gap junctional intercellular communication (GJIC) regulate many pathophysiological processes. Yet, how ER stress and GJIC regulate Cd-induced nephrotoxicity remain elusive. In this study, we treated human proximal tubule (HK-2) cells with 1 µM CdCl2 every other day for 12 days and found that Cd significantly increased cell apoptosis at 10 and 12 days. This cytotoxicity correlated with activation of ER stress and apoptotic signaling evidenced by upregulation of inositol-requiring enzyme 1 (IRE1α), splice X-box binding protein-1 (XBP-1s), and apoptosis signal-regulating kinase 1 (ASK1) proteins. Interestingly, the AKT signaling was activated at 2- and 4-day and then inhibited at 10- and 12-day of Cd treatment; by contrast, Cd decreased GJIC levels at 2- and 4-day followed by a significant increase at 10- and 12-day treatment. Activation of AKT by SC79 or inhibition of GJIC by 18α-glycyrrhetinic acid (18α-GA) completely abolished Cd-induced AKT inhibition and IRE1α-ASK1 activation. Importantly, pretreatment with ER stress inhibitor or 18α-GA significantly mitigated Cd-induced apoptosis. These results suggest that GJIC collaborates with AKT signaling and ER stress in regulating prolonged Cd-treatment-induced apoptosis in HK-2 cells.

Asunto(s)

Apoptosis/efectos de los fármacos , Cloruro de Cadmio/toxicidad , Comunicación Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Uniones Comunicantes/efectos de los fármacos , Cloruro de Cadmio/antagonistas & inhibidores , Línea Celular , Supervivencia Celular/efectos de los fármacos , Espacio Extracelular , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Proteína Oncogénica v-akt , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

A conjugated polymer probe comprised of fluorene, quinolone and benzothiazole units was designed and synthesized by the Suzuki coupling reaction. Through the studies of photophysical and thermal properties, the polymer displays blue-emitting feature and good thermal stability. A ratiometric fluorescence signal of the probe for Zn(II) was observed in ethanol with a new emission peak at 555 nm. The probe possesses a high selectivity and sensitivity for Zn(II) during familiar metal ions in ethanol. The detection limit of the probe for Zn (II) is up to 10-8 mol/L. The electron distributions of the polymer before and after bonding with Zn (II) were investigated by the Gaussian 09 software, which agreed with the experimental results. Noticeably, based on the color property of the probe with Zn(II), a series of color test paper were developed for visual detecting Zn(II) ions. This work helps to provide a platform or pattern for the development of polymer fluorescence probe in the chemosensor field.