Applicability of new degradable hypericin-polymer-conjugates as photosensitizers: principal mode of action demonstrated by in vitro models

被引：20
作者：
Feinweber, Daniela [1 ]
Verwanger, Thomas [1 ]
Brueggemann, Oliver [2 ]
Teasdale, Ian [2 ]
Krammer, Barbara [1 ]
机构：
[1] Salzburg Univ, Dept Mol Biol, Div Mol Tumor Biol, A-5020 Salzburg, Austria
[2] Johannes Kepler Univ Linz, Inst Polymer Chem, A-4060 Leonding, Austria
来源：
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES | 2014年 / 13卷 / 11期
关键词：
PHOTODYNAMIC THERAPY; ENDOPLASMIC-RETICULUM; CELL CARCINOMA; PVP-HYPERICIN; POLYPHOSPHAZENES; CANCER; TRANSPORT; DELIVERY; BIODISTRIBUTION; FORMULATIONS;
D O I：
10.1039/c4pp00251b
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Two series of water soluble novel conjugates of the photosensitizer hypericin were prepared and evaluated for their use as agents for photodynamic therapy, with covalently and non-covalently loaded hypericin on functionalised, hydrolytically degradable inorganic-organic hybrid polyphosphazenes. The conjugates showed excellent aqueous solubility and similar fluorescence spectra to pristine hypericin. Detailed in vitro investigations revealed that the substances were non-toxic in the dark over a wide concentration range, but displayed phototoxicity upon irradiation. Cell uptake studies showed rapid uptake with localization of hypericin observed in endoplasmic reticulum, Golgi complex and particularly in the lysosomes. Furthermore, a DNA fragmentation assay revealed that the photosensitizer conjugates are efficient inducers of apoptosis with some tumor cell selectivity caused by faster and enhanced accumulation in A431 than in HaCaT cells, and thus a moderately higher phototoxicity of A431 compared to HaCaT cells. These novel photosensitizer conjugates hence represent viable hydrolytically degradable alternatives for the advanced delivery of hypericin.
引用
收藏
页码：1607 / 1620
页数：14
相关论文
共 61 条
  • [11] Blank M, 2001, PHOTOCHEM PHOTOBIOL, V74, P120, DOI 10.1562/0031-8655(2001)074<0120:ACAOHI>2.0.CO
  • [12] 2
  • [13] Buhler V., 2005, Polyvinylpyrrolidone Excipients for Pharmaceuticals
  • [14] Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells
    Buytaert, E.
    Matroule, J. Y.
    Durinck, S.
    Close, P.
    Kocanova, S.
    Vandenheede, J. R.
    de Witte, P. A.
    Piette, J.
    Agostinis, P.
    [J]. ONCOGENE, 2008, 27 (13) : 1916 - 1929
  • [15] Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy
    Buytaert, Esther
    Callewaert, Geert
    Hendrickx, Nico
    Scorrano, Luca
    Hartmann, Dieter
    Missiaen, Ludwig
    Vandenheede, Jackie R.
    Heirman, Ingeborg
    Grooten, Johan
    Agostinis, Patrizia
    [J]. FASEB JOURNAL, 2006, 20 (02) : 756 - +
  • [16] Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization
    Castano, Ana P.
    Demidova, Tatiana N.
    Hamblin, Michael R.
    [J]. PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY, 2004, 1 (04) : 279 - 293
  • [17] Photodynamic therapy of with topical and systemic murine fibrosarcoma administration of hypericin
    Cavarga, I
    Brezáni, P
    Cekanová-Figurová, M
    Solár, P
    Fedorocko, P
    Migkovsky, P
    [J]. PHYTOMEDICINE, 2001, 8 (05) : 325 - 330
  • [18] Derycke ASL, 2002, INT J ONCOL, V20, P181
  • [19] Endocytosis and Intracellular Trafficking as Gateways for Nanomedicine Delivery: Opportunities and Challenges
    Duncan, Ruth
    Richardson, Simon C. W.
    [J]. MOLECULAR PHARMACEUTICS, 2012, 9 (09) : 2380 - 2402
  • [20] Polymer therapeutics as nanomedicines: new perspectives
    Duncan, Ruth
    [J]. CURRENT OPINION IN BIOTECHNOLOGY, 2011, 22 (04) : 492 - 501
1234567