RESUMEN
Selenoxide elimination reaction has been widely used in the field of organic synthesis. However, few studies have been conducted to apply this reaction in biodegradable nanomedicine. In this work, the selenoxide elimination reaction was used for cancer treatment via producing excess cellular reactive oxygen species (ROS) for the first time. The ß-seleno diesters and porphyrin derivates containing nanoparticle could be responsive to the intracellular ROS and produce acrylates through the elimination reaction. The acrylates would further deplete intracellular GSH in tumor cells and finally improved the anticancer activity in the mice tumor model. Different from traditional ROS-responsive nanomedicine, the elimination product of this reaction could regenerate cytotoxic ROS and specifically disturb the redox balance of tumor cells. This work would provide attractive avenues for the development of therapeutic strategies against cancer via synthesis of well-designed biodegradable polymers.
Asunto(s)
Antineoplásicos/farmacología , Compuestos de Organoselenio/farmacología , Estrés Oxidativo/efectos de los fármacos , Óxidos de Selenio/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Endocitosis/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Nanopartículas/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNPâ¯+â¯X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.
Asunto(s)
Neoplasias Pulmonares/terapia , Nanopartículas , Polietilenglicoles/química , Óxidos de Selenio/farmacología , Células A549 , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Quimioradioterapia/métodos , Portadores de Fármacos/química , Humanos , Neoplasias Pulmonares/patología , Óxidos de Selenio/administración & dosificaciónRESUMEN
The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 µg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator.
Asunto(s)
Antígenos de Plantas/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Polisacáridos/farmacología , Óxidos de Selenio/farmacología , Angelica/inmunología , Animales , Antígenos de Plantas/química , Células Cultivadas , Citocinas/metabolismo , Femenino , Ajo/inmunología , Inmunidad Celular/efectos de los fármacos , Inmunización , Mediadores de Inflamación/metabolismo , Macrófagos Peritoneales/inmunología , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/metabolismo , Fagocitosis/efectos de los fármacos , Polisacáridos/químicaRESUMEN
The aim of the present study was to investigate the anti-biofilm activity of biologically synthesized selenium nanoparticles (Se NPs) against the biofilm produced by clinically isolated bacterial strains compared to that of selenium dioxide. Thirty strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were isolated from various specimens of the patients hospitalized in different hospitals (Kerman, Iran). Quantification of the biofilm using microtiter plate assay method introduced 30% of S. aureus, 13% of P. aeruginosa and 17% of P. mirabilis isolates as severely adherent strains. Transmission electron micrograph (TEM) of the purified Se NPs (produced by Bacillus sp. MSh-1) showed individual and spherical nano-structure in the size range of 80-220nm. Obtained results of the biofilm formation revealed that selenium nanoparticles inhibited the biofilm of S. aureus, P. aeruginosa, and P. mirabilis by 42%, 34.3%, and 53.4%, respectively, compared to that of the non-treated samples. Effect of temperature and pH on the biofilm formation in the presence of Se NPs and SeO2 was also evaluated.
Asunto(s)
Biopelículas/efectos de los fármacos , Nanopartículas/química , Proteus mirabilis/fisiología , Pseudomonas aeruginosa/fisiología , Óxidos de Selenio/farmacología , Selenio/farmacología , Staphylococcus aureus/fisiología , Biopelículas/crecimiento & desarrollo , Humanos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Nanopartículas/ultraestructura , Tamaño de la Partícula , Proteus mirabilis/efectos de los fármacos , Proteus mirabilis/crecimiento & desarrollo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/aislamiento & purificación , Espectrometría por Rayos X , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , TemperaturaRESUMEN
The effects of selenium, putrescine, and cadmium on the contents of glucosinolates, total phenolics, flavonoids, carotenoids, chlorophyll, anthocyanin, malondialdehyde, hydrogen peroxide, and antioxidant capacities as well as gene regulation of phenolics, flavonoids, carotenoids, and glucosinolates biosynthesis were investigated in turnip plants. Selenium dioxide (SeO2) treatment significantly induced the amount of gluconasturtiin, glucobrassicanapin, glucoallysin, glucobrassicin, 4-methoxyglucobrassicin, and 4-hydroxyglucobrassicin. Cadmium chloride (CdCl2)- and putrescine-treated plants had considerably enhanced gluconasturtiin and 4-hydroxyglucobrassicin levels, respectively. Total phenolic and flavonoid content as well as antioxidant capacities were significantly increased in SeO2-treated plants. Lutein was higher in control plants followed by, in decreasing order, SeO2-, putrescine-, and CdCl2-treated plants. The chlorophyll content was significantly decreased and anthocyanin, MDA, and H2O2 levels were significantly increased with CdCl2 treatment. Moreover, plants treated with selenium and cadmium showed significant induction of genes related to glucosinolate, phenolic, and carotenoid biosynthesis. These results demonstrated that SeO2 significantly increased the contents of health-promoting compounds and enhanced the antioxidant capacities of turnip plants.