title: Tetrahydroporphyrin-tetratosylat (THPTS): A near-infrared photosensitizer for targeted and efficient photodynamic therapy (PDT) of human bladder carcinoma. An in vitro study.
abstract: BACKGROUND
  Efficacy of PDT in muscle-invasive bladder cancer is hampered by low tissue penetration of most photosensitizers by short excitation wavelength. THPTS is excitable at near-infrared (760nm) allowing tissue penetration up to 15mm. We examined the cellular effects of THPTS-PDT in human bladder cancer cells.
  
  
  METHODS
  We used four human transitional carcinoma cell lines, epithelial bladder progenitors (HBLAK) and bladder smooth muscle cells (HBSMC). We used flow cytometry to examine pharmacokinetics of THPTS, confocal laser scanning microscopy to analyze subcellular localization and production of reactive oxidative species (ROS), examined cytotoxicity and cell death pathways (qRT-PCR).
  
  
  RESULTS
  Total uptake varied between cell lines and was significantly high in HBLAK and HBSMC. Lysosomal localization was mainly seen in cancer cells and HBLAK, while THPTS was distributed throughout the cytoplasm in HBSMC. Significant ROS production was detected 30min after THPTS-PDT. Growth arrest occurred within 4h and resulted in apoptotic and necrotic cytotoxicity after 24h. Cytotoxicity was dose-dependent and specifically high in cancer cells and HBLAK and significantly low in HBSMC.
  
  
  CONCLUSIONS
  THPTS-PDT induces cellular mechanisms leading to cellular growth arrest, apoptosis and necrosis in human bladder cancer cells. These effects are only partly dependent on the total amount of THPTS uptake and rather dependent on its subcellular compartmentalization. HBSMC are hardly affected by THPTS-PDT confirming tumor specificity and safety. THPTS is a promising new photosensitizer with the unique advantage of deep tissue penetration allowing the treatment of solid tumors and warranting further animal studies.
authors.affiliation: Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany. Electronic address: mandy.berndt@medizin.uni-leipzig.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Berndt-Paetz
authors.affiliation: Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany. Electronic address: annett.weimann@medizin.uni-leipzig.de.
authors.forename: Annett
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Department of Urology, University Hospital Leipzig, Leipzig, Germany. Electronic address: nadine.sieger@uniklinik-leipzig.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Sieger
authors.affiliation: Laser Medizin Zentrum Leipzig, Leipzig, Germany. Electronic address: stanislaw.schastak@gmail.com.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Schastak
authors.affiliation: Leibniz Institute of Surface Modification (IOM), Leipzig, Germany; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, 11884, Cairo, Egypt. Electronic address: yasser_riyad@yahoo.com.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Riyad
authors.affiliation: Leibniz Institute of Surface Modification (IOM), Leipzig, Germany. Electronic address: jan.griebel@iom-leipzig.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Griebel
authors.affiliation: Department of Urology, Jahn Ferenc South Pest Teaching Hospital, Budapest, Hungary. Electronic address: vinodkumar4u2@gmail.com.
authors.forename: Vinodh K A
authors.initials: VKA
authors.lastname: Arthanareeswaran
authors.affiliation: Department of Urology, University Hospital Leipzig, Leipzig, Germany. Electronic address: jens-uwe.stolzenburg@uniklinik-leipzig.de.
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.affiliation: Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany. Electronic address: jochen.neuhaus@medizin.uni-leipzig.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011829:Radiation Dosage; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D017319:Photosensitizing Agents
keywords: Cell culture; Lysosomes; Near-infrared photosensitizer; Pharmacokinetics; Subcellular compartmentalization