Lukasz Lamch1, Urszula Bazylińska1, Julita Kulbacka2, Jadwiga Pietkiewicz3, Katarzyna Bieżuńska-Kusiak3, Kazimiera A Wilk1. 1. Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland. 2. Department of Medical Biochemistry, Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland. Electronic address: julita.kulbacka@umed.wroc.pl. 3. Department of Medical Biochemistry, Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland.
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.
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: Letícia Martins Dos Reis Lage; José Mário Barichello; Daniela Pagliara Lage; Débora Vasconcelos Costa Mendonça; Ana Maria Ravena Severino Carvalho; Marcella Rezende Rodrigues; Daniel Menezes-Souza; Bruno Mendes Roatt; Ricardo José Alves; Carlos Alberto Pereira Tavares; Eduardo Antonio Ferraz Coelho; Mariana Costa Duarte Journal: Parasitol Res Date: 2016-07-01 Impact factor: 2.289
Authors: U Bazylińska; D Wawrzyńczyk; J Kulbacka; R Frąckowiak; B Cichy; A Bednarkiewicz; M Samoć; K A Wilk Journal: Sci Rep Date: 2016-07-13 Impact factor: 4.379
Authors: Grasiele S V Tavares; Débora V C Mendonça; Isabela A G Pereira; João A Oliveira-da-Silva; Fernanda F Ramos; Daniela P Lage; Amanda S Machado; Lívia M Carvalho; Thiago A R Reis; Luísa Perin; Ana Maria R S Carvalho; Flaviano M Ottoni; Fernanda Ludolf; Camila S Freitas; Raquel S Bandeira; Alessandra M Silva; Miguel A Chávez-Fumagalli; Mariana C Duarte; Daniel Menezes-Souza; Ricardo J Alves; Bruno M Roatt; Eduardo A F Coelho Journal: Parasite Date: 2020-04-30 Impact factor: 3.000