Mechanisms in photodynamic therapy: Part three- Photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction

被引:443
作者
Castano, Ana P. [1 ,2 ]
Demidova, Tatiana N. [1 ,3 ]
Hamblin, Michael R. [1 ,2 ,4 ]
机构
[1] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA
[2] Harvard Univ, Dept Dermatol, Sch Med, Cambridge, MA 02138 USA
[3] Tufts Univ, Cell Mol & Dev Biol Program, Medford, MA USA
[4] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA
基金
美国国家卫生研究院;
关键词
Photodynamic therapy; Cancer; Pharmacokinetics; Biodistribution; Cellular destruction; Vascular shutdown; Anti-tumor immunity;
D O I
10.1016/S1572-1000(05)00060-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as cancer therapy, some of its most successful applications are for non-malignant disease. The majority of mechanistic research into PDT, however, is still directed towards anti-cancer applications. In the final part of series of three reviews, we will cover the possible reasons for the well-known tumor localizing properties of photosensitizers (PS). When PS are injected into the bloodstream they bind to various serum proteins and this can affect their phamacokinetics and biodistribution. Different PS can have very different pharmacokinetics and this can directly affect the illumination parameters. Intravenously injected PS undergo a transition from being bound to serum proteins, then bound to endothelial cells, then bound to the adventitia of the vessels, then bound either to the extracellular matrix or to the cells within the tumor, and finally to being cleared from the tumor by lymphatics or blood vessels, and excreted either by the kidneys or the liver. The effect of PDT on the tumor largely depends at which stage of this continuous process light is delivered. The anti-tumor effects of PDT are divided into three main mechanisms. Powerful anti-vascular effects can lead to thrombosis and hemorrhage in tumor blood vessels that subsequently lead to tumor death via deprivation of oxygen and nutrients. Direct tumor cell death by apoptosis or necrosis can occur if the PS has been allowed to be taken up by tumor cells. Finally the acute inflammation and release of cytokines and stress response proteins induced in the tumor by PDT can lead to an influx of leukocytes that can both contribute to tumor destruction as well as to stimulate the immune system to recognize and destroy tumor cells even at distant locations. (C) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:91 / 106
页数:16
相关论文
共 125 条
  • [31] Dolmans DEJGJ, 2002, CANCER RES, V62, P4289
  • [32] Plasma pharmacokinetics and tissue distribution in CD2F1 mice of Pc4 [NSC 676418], a silicone phthalocyanine photodynamic sensitizing agent
    Egorin, MJ
    Zuhowski, EG
    Sentz, DL
    Dobson, JM
    Callery, PS
    Eiseman, JL
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1999, 44 (04) : 283 - 294
  • [33] Motexafin gadolinium: a redox-active tumor selective agent for the treatment of cancer
    Evens, AM
    [J]. CURRENT OPINION IN ONCOLOGY, 2004, 16 (06) : 576 - 580
  • [34] Evstigneeva Rima P., 2003, Current Medicinal Chemistry - Anti-Cancer Agents, V3, P383, DOI 10.2174/1568011033482260
  • [35] FERRARIO A, 1992, CANCER RES, V52, P2890
  • [36] FIGGE FHJ, 1948, P SOC EXP BIOL MED, V68, P640
  • [37] FINGAR VH, 1990, CANCER RES, V50, P2599
  • [38] THE EFFECTS OF THROMBOXANE INHIBITORS ON THE MICROVASCULAR AND TUMOR RESPONSE TO PHOTODYNAMIC THERAPY
    FINGAR, VH
    SIEGEL, KA
    WIEMAN, TJ
    DOAK, KW
    [J]. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1993, 58 (03) : 393 - 399
  • [39] THE EFFECTS OF PHOTODYNAMIC THERAPY USING DIFFERENTLY SUBSTITUTED ZINC PHTHALOCYANINES ON VESSEL CONSTRICTION, VESSEL LEAKAGE AND TUMOR RESPONSE
    FINGAR, VH
    WIEMAN, TJ
    KARAVOLOS, PS
    DOAK, KW
    OUELLET, R
    VANLIER, JE
    [J]. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1993, 58 (02) : 251 - 258
  • [40] OXYGEN-CONSUMPTION AND DIFFUSION EFFECTS IN PHOTODYNAMIC THERAPY
    FOSTER, TH
    MURANT, RS
    BRYANT, RG
    KNOX, RS
    GIBSON, SL
    HILF, R
    [J]. RADIATION RESEARCH, 1991, 126 (03) : 296 - 303