RESUMO
In this study, we aimed to investigate ozonized oil nanoemulsions (OZNEs) as a radiosensitizer within B-16 melanoma and OV-90 ovarian cells under X-ray irradiation in vitro. Radiation sensitivity of OZNE treated B-16 melanoma cells and OV-90 ovarian cells were evaluated by performing cell cycle analysis, Reactive Oxygen Species (ROS) and ɣ-H2AX assays by flow cytometry. OZNEs induced G0-1 phase arrest of B-16 melanoma cells for all radiation doses and G2/M arrest for 8 Gy and 15 Gy doses. OZNE treated B-16 melanoma and OV-90 ovarian cells induced DNA damage via the increase in ROS production, as well as significant increase in the expression of ɣ-H2AX under even low doses of radiation (2 Gy). Thus, OZNEs are suggested to help to optimize cancer RT as a radiosensitizer and further studies will significantly outperform recent advances in this field.
Assuntos
Melanoma , Radiossensibilizantes , Apoptose , Linhagem Celular Tumoral , Dano ao DNA , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Melanoma/metabolismo , Radiação Ionizante , Radiossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
In this study, Response Surface Methodology (RSM) was used to model and optimize the electrospinning parameters to obtain poly(2-hydroxylethyl methacrylate) (pHEMA) nanofibers which is challenging in terms of evaluating the optimum conditions in nanofiber production. A second order (quadratic model) polynomial function was used for correlation between electrospinning parameters (flow rate, applied voltage, polymer/ethanol concentration) and average fiber diameter. An electro-spinning set-up was used to fabricate nanofibers and scanning electron microscopy (SEM) was used to determine the morphology and the size of the nanofibers with diameter ranging from 211 nm to 1661 nm. Results concluded that the concentration of polymer solution played an important role in distribution of fiber diameter. Based on RSM, the optimum pHEMA fibers with 245±35 nm diameter were collected at 13 µL/min flow rate, 12 kV applied voltage at an ethanol:pHEMA ratio of 1.76.
RESUMO
Intraoperative bioprinting (IOB), which refers to the bioprinting process performed on a live subject in a surgical setting, has made it feasible to directly deliver gene-activated matrices into craniomaxillofacial (CMF) defect sites. In this study, we demonstrated a novel approach to overcome the current limitations of traditionally fabricated non-viral gene delivery systems through direct IOB of bone constructs into defect sites. We used a controlled co-delivery release of growth factors from a gene-activated matrix (an osteogenic bioink loaded with plasmid-DNAs (pDNA)) to promote bone repair. The controlled co-delivery approach was achieved from the combination of platelet-derived growth factor-B encoded plasmid-DNA (pPDGF-B) and chitosan-nanoparticle encapsulating pDNA encoded with bone morphogenetic protein-2 (CS-NPs(pBMP2)), which facilitated a burst release of pPDGF-B in 10 days, and a sustained release of pBMP-2 for 5 weeks in vitro. The controlled co-delivery approach was tested for its potential to repair critical-sized rat calvarial defects. The controlled-released pDNAs from the intraoperatively bioprinted bone constructs resulted in â¼40% bone tissue formation and â¼90% bone coverage area at 6 weeks compared to â¼10% new bone tissue and â¼25% total bone coverage area in empty defects. The delivery of growth factors incorporated within the intraoperatively bioprinted constructs could pose as an effective way to enhance bone regeneration in patients with cranial injuries in the future.
Assuntos
Bioimpressão , Proteína Morfogenética Óssea 2 , Animais , Bioimpressão/métodos , Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea/genética , Osso e Ossos , Técnicas de Transferência de Genes , Humanos , Osteogênese , RatosRESUMO
Salinomycin has been introduced as a novel alternative to traditional anti-cancer drugs. The aim of this study was to test a strategy designed to deliver salinomycin to glioblastoma cells in vitro. Salinomycin-encapsulated polysorbate 80-coated poly(lactic-co-glycolic acid) nanoparticles (P80-SAL-PLGA) were prepared and characterized with respect to particle size, morphology, thermal properties, drug encapsulation efficiency and controlled salinomycin-release behaviour. The in vitro cellular uptake of P80-SAL-PLGA (5 and 10 µM) or uncoated nanoparticles was assessed in T98G human glioblastoma cells, and the cell viability was investigated with respect to anti-growth activities. SAL, which was successfully transported to T98G glioblastoma cells via P80 coated nanoparticles (â¼14% within 60 min), greatly decreased (p < 0.01) the cellular viability of T98G cells. Substantial morphological changes were observed in the T98G cells with damaged actin cytoskeleton. Thus, P80-SAL-PLGA nanoparticles induced cell death, suggesting a potential therapeutic role for this salinomycin delivery system in the treatment of human glioblastoma.
Assuntos
Glioblastoma/tratamento farmacológico , Ácido Láctico , Ácido Poliglicólico , Polissorbatos , Piranos , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polissorbatos/química , Polissorbatos/farmacologia , Piranos/química , Piranos/farmacologiaRESUMO
Progress in cancer treatment remains challenging because of the great nature of tumor cells to be drug resistant. However, advances in the field of nanotechnology have enabled the delivery of drugs for cancer treatment by passively and actively targeting to tumor cells with nanoparticles. Dramatic improvements in nanotherapeutics, as applied to cancer, have rapidly accelerated clinical investigations. In this review, drug-targeting systems using nanotechnology and approved and clinically investigated nanoparticles for cancer therapy are discussed. In addition, the rationale for a nanotechnological approach to cancer therapy is emphasized because of its promising advances in the treatment of cancer patients.