title: Polymeric micelles for enhanced Photofrin II ® delivery, cytotoxicity and pro-apoptotic activity in human breast and ovarian cancer cells.
abstract: BACKGROUND
  Searching for photodynamic therapy (PDT) - effective nanocarriers which enable a photosensitizer to be selectively delivered to tumor cells with enhanced bioavailability and diminished dark cytotoxicity is of current interest. The main objective of this study is to evaluate newly designed mixed polymeric micelles based on Pluronics P123 and F127 for the improved delivery of Photofrin II(®) (Ph II(®)) to circumvent unfavorable effects overcoming multidrug resistance (MDR) in tumor cells - in breast MCF-7/WT (caspase-3 deficient) and ovarian SKOV-3 (resistant to chemotherapy).
  
  
  METHODS
  Ph II(®)-loaded micelles were obtained and analyzed for size and morphology, solubilization efficiency, physical stability and in vitro drug release. Intracellular uptake, reactive oxygen species (ROS) generation, mitochondrial oxidoreductive potential and proapoptotic activity (TUNEL assay) studies were evaluated in the examined cancer cells. The preliminary biocompatibility characteristics of all nanocarriers was determined by assessment of their hemolytic activity in human erythrocytes and dark toxicity in cancer cells.
  
  
  RESULTS
  Dynamic light scattering (DLS) and atomic force microscopy (AFM) confirmed that almost monodisperse, sphere-shaped and nanosized (DH<20 nm) carriers were developed. Biological studies after photodynamic reaction (PDR) with encapsulated Ph II(®) revealed increased ROS level, malondialdehyde (MDA) concentration and protein damage in SKOV-3 and MCF-7/WT cells in comparison to treatment with free Ph II(®). Numerous apoptotic cells were detected after nano-therapy in both cell lines, with observed significant morphological disorders in ovarian cancer cells. In the case of encapsulated Ph II(®) only negligible disruption of human erythrocytes and cancer cells was observed.
  
  
  CONCLUSIONS
  The obtained biocompatible long-lasting nanocarriers significantly enhance the Photofrin II(®) photodynamic effect and apoptosis in both SKOV-3 and MCF-7/WT cell lines.
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Lamch
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Bazylińska
authors.affiliation: Department of Medical Biochemistry, Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland. Electronic address: julita.kulbacka@umed.wroc.pl.
authors.forename: Julita
authors.initials: J
authors.lastname: Kulbacka
authors.affiliation: Department of Medical Biochemistry, Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Pietkiewicz
authors.affiliation: Department of Medical Biochemistry, Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bieżuńska-Kusiak
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Kazimiera A
authors.initials: KA
authors.lastname: Wilk
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects*; D004058:Diffusion; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D010789:Phototherapy / Q000379:methods*; D020442:Poloxamer / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D008823:Micelles; D017319:Photosensitizing Agents; D020442:Poloxamer; D017323:Dihematoporphyrin Ether
keywords: Cancer cells; Hemolytic activity; Mixed Pluronic micelles; Photodynamic therapy; Photofrin II(®); Release characteristics