title: Development of novel radiochemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids.
abstract: Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the different plants, including green tea, and it is widely recognized as co-adjuvant in cancer therapy. Here we describe the synthesis of biocompatible, catechin-loaded and gelatin-conjugated CNTs (Gel_CT_CNTs) with anticancer properties and demonstrate their potential for the eradication of prostate CSCs in combination with X-ray irradiation. Gel_CT_CNTs showed a significant enhancement of in vitro anticancer activity as compared to catechin alone. Moreover, treatment of prostate cancer cells with Gel_CT_CNT nanohybrids inhibited the tumorigenic cell population defined by a high aldehyde dehydrogenase (ALDH) activity. A combination of X-ray irradiation and treatment with Gel_CT_CNTs caused a decrease in the protein level of stem cell-related transcription factors and regulators including Nanog, Oct4 and β-catenin and led to an increase of cancer cell radiosensitivity as demonstrated by clonogenic and spherogenic cell survival assays. Taken together, our results suggest that a combination of irradiation and Gel_CT_CNTs can be potentially used for the radiosensitization and eradication of prostate CSC populations.
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, Dresden, Germany.|Leibniz Institute of Solid State and Material Research Dresden, Dresden, Germany.
authors.forename: Arturo
authors.initials: A
authors.lastname: Castro Nava
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Monica
authors.initials: M
authors.lastname: Cojoc
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Peitzsch
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata Di Rende, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Kurth
authors.affiliation: Department of Urology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fuessel
authors.affiliation: Department of Urology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Kati
authors.initials: K
authors.lastname: Erdmann
authors.affiliation: Leibniz Institute of Solid State and Material Research Dresden, Dresden, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Kunhardt
authors.affiliation: Children's Cancer Institute Australia Lowy Cancer Research Centre, UNSW, Sydney, Australia.|Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Orazio
authors.initials: O
authors.lastname: Vittorio
authors.affiliation: Leibniz Institute of Solid State and Material Research Dresden, Dresden, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hampel
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, Dresden, Germany.|German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubrovska
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis*; D002392:Catechin / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059248:Chemoradiotherapy / Q000379:methods; D004339:Drug Compounding; D005780:Gelatin / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D037742:Nanotubes, Carbon; D011838:Radiation-Sensitizing Agents; D002392:Catechin; D005780:Gelatin; D000444:Aldehyde Dehydrogenase
keywords: carbon nanotubes; catechin; radiosensitization; tumor-initiating cells