Selective Photodetection and Photodynamic Therapy for Prostate Cancer through Targeting of Proteolytic Activity

被引:13
|
作者
Zuluaga, Maria-Fernanda [1 ]
Sekkat, Nawal [1 ]
Gabriel, Doris [1 ]
van den Bergh, Hubert [2 ]
Lange, Norbert [1 ]
机构
[1] Univ Lausanne, Univ Geneva, Dept Pharmaceut & Biopharmaceut, Sch Pharmaceut Sci, CH-1211 Geneva 4, Switzerland
[2] Swiss Fed Inst Technol EPFL, Photomed Grp, Inst Bioengn, Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
UROKINASE-PLASMINOGEN-ACTIVATOR; POLYMERIC PHOTOSENSITIZER PRODRUGS; CELLS; RECEPTOR;
D O I
10.1158/1535-7163.MCT-12-0780
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Frequent side effects of radical treatment modalities and the availability of novel diagnostics have raised the interest in focal therapies for localized prostate cancer. To improve the selectivity and therapeutic efficacy of such therapies, we developed a minimally invasive procedure based on a novel polymeric photosensitizer prodrug sensitive to urokinase-type plasminogen activator (uPA). The compound is inactive in its prodrug form and accumulates passively at the tumor site by the enhanced permeability and retention effect. There, the prodrug is selectively converted to its photoactive form by uPA, which is overexpressed by prostate cancer cells. Irradiation of the activated photosensitizer exerts a tumor-selective phototoxic effect. The prodrug alone (8 mu mol/L) showed no toxic effect on PC-3 cells, but upon irradiation the cell viability was reduced by 90%. In vivo, after systemic administration of the prodrug, PC-3 xenografts became selectively fluorescent. This is indicative of the prodrug accumulation in the tumor and selective local enzymatic activation. Qualitative analysis of the activated compound confirmed that the enzymatic cleavage occurred selectively in the tumor, with only trace amounts in the neighboring skin or muscle. Subsequent photodynamic therapy studies showed complete tumor eradication of animals treated with light (150 J/cm(2) at 665 nm) 16 hours after the injection of the prodrug (7.5 mg/kg). These promising results evidence the excellent selectivity of our prodrug with the potential to be used for both imaging and therapy for localized prostate cancer. Mol Cancer Ther; 12(3); 306-13. (C)2012 AACR.
引用
收藏
页码:306 / 313
页数:8
相关论文
共 50 条
  • [41] Silicon Phthalocyanines Functionalized with Axial Substituents Targeting PSMA: Synthesis and Preliminary Assessment of Their Potential for PhotoDynamic Therapy of Prostate Cancer
    Capozza, Martina
    Digilio, Giuseppe
    Gagliardi, Michela
    Tei, Lorenzo
    Marchesi, Stefano
    Terreno, Enzo
    Stefania, Rachele
    CHEMMEDCHEM, 2024, 19 (22)
  • [42] Selective local control of bile duct cancer by photodynamic therapy
    Berr, F
    Tannapfel, A
    Pahernik, S
    Wiedmann, M
    Lange, K
    Halm, U
    Dellian, M
    Goetz, A
    Wittekind, C
    Mossner, J
    GASTROENTEROLOGY, 1997, 112 (04) : A538 - A538
  • [43] Targeting gastrin-releasing peptide receptors of prostate cancer cells for photodynamic therapy with a phthalocyanine-bombesin conjugate
    Dubuc, Celena
    Langlois, Rejean
    Benard, Francois
    Cauchon, Nicole
    Klarskov, Klaus
    Tone, Paul
    van Lier, Johan E.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (07) : 2424 - 2427
  • [44] Mreg Activity in Tumor Response to Photodynamic Therapy and Photodynamic Therapy-Generated Cancer Vaccines
    Korbelik, Mladen
    Banath, Judith
    Zhang, Wei
    CANCERS, 2016, 8 (10)
  • [45] SELECTIVE DESTRUCTION OF EXPERIMENTAL COLON CANCER USING PHOTODYNAMIC THERAPY
    BARR, H
    TRALAU, CJ
    LEWIN, M
    CLARK, CG
    BOWN, SG
    BOULOS, PB
    BRITISH JOURNAL OF SURGERY, 1988, 75 (06) : 611 - 612
  • [46] SELECTIVE DESTRUCTION OF EXPERIMENTAL COLON CANCER USING PHOTODYNAMIC THERAPY
    BARR, H
    TRALAU, CJ
    LEWIN, M
    CLARK, CG
    BOULOS, PB
    BOWN, SG
    LASERS IN SURGERY AND MEDICINE, 1988, 8 (02) : 180 - 180
  • [47] Targeting the prostate-specific membrane antigen for prostate cancer therapy
    Buehler, Patrick
    Wolf, Philipp
    Elsaesser-Beile, Ursula
    IMMUNOTHERAPY, 2009, 1 (03) : 471 - 481
  • [48] ENHANCEMENT OF VITAMIN D BASED THERAPY FOR PROSTATE CANCER TREATMENT BY SELECTIVE TARGETING OF 24-HYDROXYLASE
    Tannour-Louet, Mounia
    Lewis, Shaye
    Stewart, Julie
    Sahin, Aysegul
    Han, Shuo
    Addai, Josephine
    Lamb, Dolores
    JOURNAL OF ANDROLOGY, 2010, : 45 - 45
  • [49] Bacteriophage Bionanowire as a Carrier for Both Cancer-Targeting Peptides and Photosensitizers and its use in Selective Cancer Cell Killing by Photodynamic Therapy
    Gandra, Naveen
    Abbineni, Gopal
    Qu, Xuewei
    Huai, Yanyan
    Wang, Li
    Mao, Chuanbin
    SMALL, 2013, 9 (02) : 215 - 221
  • [50] The evolution of prostate cancer therapy: targeting the androgen receptor
    Aragon-Ching, Jeanny B.
    FRONTIERS IN ONCOLOGY, 2014, 4