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Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P) H multi-photon fluorescence lifetime imaging

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Nano Research 2019年第5期12卷 991-998页

作者： Ana R.Faria Oscar F.Silvestre Christian Maibohm Ricardo M.R.Adao Bruno F.B.Silva Jana B.Nieder Department of Nanophotonics Ultrafast Bio- and Nanophotonics GroupINL - International Iberian Nanotechnology LaboratoryAv.Mestre Jose Veiga s/n4715-330 BragaPortugal Department of Life Sciences INL-International Iberian Nanotechnology LaboratoryAv.Mestre Jose Veiga s/n4715-330 BragaPortugal

Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen ***,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic *** uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment *** monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer *** in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free *** novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.

关键词： cubosomes mitoch on dria reactive oxyge n species elesclomol NAD(P)H fluoresce nee lifetime anticancer therapy

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Mitochondrial uncoupling protein 2 and pancreatic cancer:A new potential target therapy

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World Journal of Gastroenterology 2015年第11期21卷 3232-3238页

作者： Massimo Donadelli Ilaria Dando Elisa Dalla Pozza Marta Palmieri Department of Life and Reproduction Sciences Biochemistry SectionUniversity of Verona

Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal ***,the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this *** poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis,early metastasis of tumor,and resistance to almost all tested cytotoxic *** this respect,the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic *** studies have shown that the mitochondrial uncoupling protein 2(UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal *** addition,recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming,including aerobic glycolysis stimulation,promotion of cancer *** observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic *** this editorial,recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.

关键词： Uncoupling protein 2 Target therapy Reactive oxyge

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