RESUMEN
Plant cell walls (CWs) with complex macromolecular structures can surround and protect cells from a variety of harsh environmental conditions such as pathogens, herbivores, and trace metals. Here, a novel strategy for in situ imaging of plant cell walls was developed to evaluate heavy metal pollution via thiolated full-color emissive carbon-dots (F-CDs) targeting Pb(ii)-adsorbed onion cell walls. The thiolated F-CDs with excellent optical properties from red light to blue light were synthesized through a facile electrochemical approach using new precursors of luminol and l-tryptophan and further modified with l-cysteine. Based on a strong covalent interaction of Pb(ii) and thiolated F-CDs, we achieved in situ fluorescence imaging for the Pb(ii) adsorbed on CWs, which showed enhanced red, blue and green multi-color fluorescence (FL) on CWs with increased Pb(ii)-ion content. In contrast, multi-color fluorescence on cytoplasm diminished, attributed to F-CDs targeting and accumulating on the cytoskeleton which thus limited F-CD diffusion into protoplasm. Therefore, in situ fluorescent images for CWs can demonstrate heavy metal contamination degrees in plant cells. This facile and undamaging protocol will be beneficial for investigating heavy metal migration into the protoplast and fast evaluation of food quality and safety.
Asunto(s)
Carbono/química , Pared Celular/química , Colorantes Fluorescentes/química , Plomo/análisis , Puntos Cuánticos/química , Adsorción , Color , Colorimetría/métodos , Células Endoteliales/química , Fluorescencia , Contaminación de Alimentos/análisis , Tecnología Química Verde/métodos , Plomo/química , Cebollas/químicaRESUMEN
Poor bioavailability and non-specificity of chemotherapeutic agents are major challenges in breast cancer treatment. Antibodies and small molecules that block cell signaling pathways have shown promise in the clinic, but their application is also limited by the high costs and treatment dosages required. Novel therapies that aim to rapidly and specifically target malignant cells with long-lasting impact in the tumor microenvironment may ultimately improve clinical outcome in cancer patients. Here, we demonstrate that epidermal growth factor receptor (EGFR)-targeting GE11 peptides conjugated with PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles can be used to effectively deliver an anti-cancer agent, curcumin, into EGFR-expressing MCF-7 cells in vitro and in vivo. Treatment of breast cancer cells and tumor-bearing mice with these curcumin-loaded nanoparticles gave rise to reduced phosphoinositide 3-kinase signaling, decreased cancer cell viability, attenuated drug clearance from the circulation, and suppressed tumor burden compared with free curcumin or non-EGFR targeting nanoparticles. The targeted nanoscale drug delivery system we describe here may provide a new strategy for the design of targeted cancer therapy vectors. Our study provides evidence that the efficacy of pharmacologic anti-cancer agents can be enhanced through their delivery in the form of modified nanoparticles that effectively target specific malignant cell types.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Curcumina/administración & dosificación , Portadores de Fármacos , Receptores ErbB/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Animales , Femenino , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas , Fosfatidilinositol 3-Quinasas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Selenium nanoparticles (Se NPs) have attracted increasing interest in recent decades because of their anticancer, immunoregulation, and drug carrier functions. In this study, GE11 peptide-conjugated Se NPs (GE11-Se NPs), a nanosystem targeting EGFR over-expressed cancer cells, were synthesized for oridonin delivery to achieve enhanced anticancer efficacy. Oridonin loaded and GE11 peptide conjugated Se NPs (GE11-Ori-Se NPs) were found to show enhanced cellular uptake in cancer cells, which resulted in enhanced cancer inhibition against cancer cells and reduced toxicity against normal cells. After accumulation into the lysosomes of cancer cells and increase of oridonin release under acid condition, GE11-Ori-Se NPs were further transported into cytoplasm after the damage of lysosomal membrane integrity. GE11-Ori-Se NPs were found to induce cancer cell apoptosis by inducting reactive oxygen species (ROS) production, activating mitochondria-dependent pathway, inhibiting EGFR-mediated PI3K/AKT and inhibiting Ras/Raf/MEK/ERK pathways. GE11-Se NPs were also found to show active targeting effects against the tumor tissue in esophageal cancer bearing mice. And in nude mice xenograft model, GE11-Ori-Se NPs significantly inhibited the tumor growth via inhibition of tumor angiogenesis by reducing the angiogenesis-marker CD31 and activation of the immune system by enhancing IL-2 and TNF-α production. The selenium contents in mice were found to accumulate into liver, tumor, and kidney, but showed no significant toxicity against liver and kidney. This cancer-targeted design of Se NPs provides a new strategy for synergistic treating of cancer with higher efficacy and reduced side effects, introducing GE11-Ori-Se NPs as a candidate for further evaluation as a chemotherapeutic agent for EGFR over-expressed esophageal cancers.
Asunto(s)
Antineoplásicos/farmacología , Diterpenos de Tipo Kaurano/farmacología , Receptores ErbB/antagonistas & inhibidores , Péptidos/farmacología , Selenio/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/administración & dosificación , Diterpenos de Tipo Kaurano/farmacocinética , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Interleucina-2/biosíntesis , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Nanopartículas/química , Péptidos/administración & dosificación , Péptidos/farmacocinética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Selenio/farmacocinética , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Selenium nanoparticles (Se NPs) have been served as promising materials for biomedical applications, especially for cancer treatment. The anti-cancer effects of Se NPs against cancer cells have been widely studied in recent years, but whether Se NPs can induce the changes of cell membrane bio-mechanical properties in cancer cells still remain unexplored. In this Letter, we prepared Se NPs for investigating the intracellular localization of Se NPs in MCF-7 cells and determined the effects of Se NPs on apoptosis and necrosis in MCF-7 cells. Especially, we reported for the first time about the effects of Se NPs on the bio-mechanical properties of cancer cells and found that Se NPs could remarkably decrease the adhesion force and Young's modulus of MCF-7 cells. To further understand the potential mechanisms about how Se NPs affect the bio-mechanical properties of MCF-7 cells, we also investigated the expression of CD44 molecules, the structure and the amounts of F-actin. The results indicated that the decreased adhesion force between AFM tip and cell membrane was partially due to the changes of membrane molecules induced by Se NPs, such as the down-regulation of trans-membrane CD44 molecules. Additionally, the decrease of Young's modulus of MCF-7 cells was due to the dis-organization and down-regulation of F-actin induced by Se NPs. These results collectively suggested that cell membrane was of vital importance in Se NPs induced toxicity in cancer cells, which could be served as a potential target for cancer treatment by Se NPs.
Asunto(s)
Actinas/metabolismo , Nanopartículas/química , Nanopartículas/uso terapéutico , Selenio/química , Selenio/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Humanos , Receptores de Hialuranos/biosíntesis , Lisosomas/química , Lisosomas/metabolismo , Células MCF-7 , Microscopía de Fuerza AtómicaRESUMEN
Germanium (Ge) is considered to play a key role in the pharmacological effects of some medicinal plants. Here, two new Ge(IV)-polyphenol complexes were synthesized and measured for their potential biological activities. The results indicated that these Ge(IV)-polyphenol complexes possessed great anti-oxidative activities, both showing stronger hydroxyl scavenging effects than their corresponding ligands. We also demonstrated the strong intercalating abilities of Ge(IV)-polyphenol complexes into calf thymus-DNA molecules. In addition, these two Ge(IV)-polyphenol complexes showed strong proliferative inhibition effect on HepG2 cancer cells. Moreover, the morphological changes in HepG2 cells induced by Ge(IV)-polyphenol complexes were detected by atomic force microscopy. All these results collectively suggested that Ge(IV)-polyphenol complexes could be served as promising pharmacologically active substances against cancer treatment.
Asunto(s)
Antineoplásicos/farmacología , Germanio/química , Compuestos Organometálicos/farmacología , Polifenoles/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-ActividadRESUMEN
Quercetin is a popular flavonoid in plant foods, herbs, and dietary supplement. Germanium, a kind of trace elements, can enhance the body immunity. This study investigated the hydroxyl-radical-scavenging mechanism of the quercertin-germanium (IV) (Qu-Ge) complex to human erythrocytes, especially the effects on ultrastructure and mechanical properties of cell membrane, plasma membrane potential and intracellular free Ca(2+) concentration. Results showed that QuGe(2), a kind of the Qu-Ge complex, could reduce the oxidative damage of erythrocytes, change the cell-surface morphology, and partly recover the disruption of plasma membrane potential and intracellular free Ca(2+) level. Atomic force microscopy (AFM) was used to characterize the changes of the cell morphology, cell-membrane ultrastructure and biophysical properties at nanoscalar level. QuGe(2) has triggered the antioxidative factor to inhibit cellular damage. These results can improve the understanding of hydroxyl-radical-scavenging mechanism of human erythrocytes induced by the Qu-Ge complex, which can be potentially developed as a new antioxidant for treatment of oxidative damage.
Asunto(s)
Complejos de Coordinación/farmacología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Depuradores de Radicales Libres/farmacología , Germanio/farmacología , Radical Hidroxilo/sangre , Quercetina/farmacología , Antioxidantes/farmacología , Calcio/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Células Cultivadas , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Citometría de Flujo , Humanos , Potenciales de la Membrana/efectos de los fármacos , Microscopía de Fuerza Atómica , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Photothermal cancer therapy, as a prospective approach for local cancer treatment, is attracting increasing interests. In this paper, gold nanorods were conjugated with folate (folate/AuNRs), and their photothermal effects on hepatocellular carcinoma cell line (HepG2) using MTT assay, flow cytometry, as well as on the cellular morphology, cytoskeleton, cell surface adhesion, and stiffness detected at subcellular level by an atomic force microscope (AFM) were investigated. The results indicated that near-infrared laser-induced hyperthermia of folate/AuNRs could break the cell membrane integrity and homeostasis and then lead to the depolymerization of cytoskeleton and influx of intracellular Ca(2+). Thus, folate/AuNRs can be as effective and promising nanomaterials for photothermal therapy of folate receptor bearing tumor.