title: Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism.
abstract: Pancreatic cancer (PC) is one of the most lethal solid tumor in humans, with an overall 5-year survival rate of less than 5%. Thermally active carbon nanotubes have already brought to light promising results in PC research and treatment. We report here the construct of a nano-biosystem based on multi-walled carbon nanotubes and polyethylene glycol (PEG) molecules validated through AFM, UV-Vis and DLS. We next studied the photothermal effect of these PEG-ylated multi-walled carbon nanotubes (5, 10 and 50 μg/mL, respectively) on pancreatic cancer cells (PANC-1) and further analyzed the molecular and cellular events involved in cell death occurrence. Using cell proliferation, apoptosis, membrane polarization and oxidative stress assays for ELISA, fluorescence microscopy and flow cytometry we show here that hyperthermia following MWCNTs-PEG laser mediated treatment (808 nm, 2W) leads to mitochondrial membrane depolarization that activates the flux of free radicals within the cell and the oxidative state mediate cellular damage in PC cells via apoptotic pathway. Our results are of decisive importance especially in regard with the development of novel nano-biosystems capable to target mitochondria and to synergically act both as cytotoxic drug as well as thermally active agents in order to overcome one of the most common problem met in oncology, that of intrinsic resistance to chemotherapeutics.
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Teodora
authors.initials: T
authors.lastname: Mocan
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Cristian T
authors.initials: CT
authors.lastname: Matea
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Iulia
authors.initials: I
authors.lastname: Cojocaru
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Ioana
authors.initials: I
authors.lastname: Ilie
authors.affiliation: 2. Department of Pathology, University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, 3-5 Manastur Street, 400372 Cluj-Napoca, Romania.
authors.forename: Flaviu A
authors.initials: FA
authors.lastname: Tabaran
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Florin
authors.initials: F
authors.lastname: Zaharie
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Cornel
authors.initials: C
authors.lastname: Iancu
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Dana
authors.initials: D
authors.lastname: Bartos
authors.affiliation: 1. Gastroenterology Institute; Department of Nanomedicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca, Romania;
authors.forename: Lucian
authors.initials: L
authors.lastname: Mocan
keywords: PEG functionalization; apoptosis; carbon nanotubes; mitochondrial therapy.; pancreatic cancer; photothermal ablation