Comparative characterization of the efficiency and cellular pharmacokinetics of Foscan-® and Foslip®-based photodynamic treatment in human biliary tract cancer cell lines
Comparative characterization of the efficiency and cellular pharmacokinetics of Foscan-® and Foslip®-based photodynamic treatment in human biliary tract cancer cell lines
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DOI：
10.1039/b617659c
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Berr, Frieder
中科院分区：
文献类型：
--
作者：
Kiesslich, Tobias;Berlanda, Juergen;Berr, Frieder
由于肝门部胆管癌预后差，治疗选择有限，寻找新的治疗方法是一个重要的课题。光动力疗法(PDT)作为姑息性或新辅助内窥镜治疗不能切除的肺门周围癌，提高了患者的生活质量和生存时间，但因杀瘤深度不足(仅限于肿瘤狭窄周围4 mm)而不能根治原发肿瘤。使用间四羟基苯基氯(MTHPC)和较高波长(650-660 nm)的光激活可为胰腺癌的PDT提供较高的杀瘤深度(10 Mm)，而CC应产生类似的杀瘤深度。本研究在由两种胆管癌细胞(GBC、胆囊癌和BDC、胆管癌细胞)组成的体外模型系统中，研究了mTHPC在溶剂型制剂(FOSCAN(R))和脂质体(水溶性)制剂(FOSLIP(R))中的光动力学特性。研究了Foscan(R)和Foslip(R)的暗毒性、光动力效率、时间依赖的摄取和保留以及细胞内定位。结果表明，当mTHPC的浓度为600ngml(-1)，照射剂量为1.5J cm(-2)(660+/-10 nm)时，对胆管癌细胞的杀伤率约为90%。将胎牛血清(FBS)添加到培养介质中，并对吸收和光毒性特性进行分析，结果表明，两种光敏剂配方都与血清蛋白质组分结合在一起，即在存在FBS的情况下，FOSCAN(R)和FOSLIP(R)之间没有区别。激光扫描荧光显微镜显示，两种敏感剂的核周定位模式相似。这项研究证明了mTHPC用于治疗胆道恶性肿瘤的潜力，并提供了证据，证明Foslip(R)是mTHPC的等量水溶性制剂，应该可以简化静脉注射，从而简化mTHPC的临床使用。
Due to the poor prognosis and limited management options for perihilar cholangiocarcinoma (CC) the development of alternatives for treatment is an important topic. Photodynamic therapy (PDT) with porfimer as palliative or neoadjuvant endoscopic treatment of non-resectable perihilar CC has improved quality of life and survival time, but cannot eradicate the primary tumors because of inadequate tumoricidal depth (4 mm only around the tumor stenoses). The use of meta-tetrahydroxy-phenyl chlorin (mTHPC) and photoactivation at higher wavelengths (650-660 nm) provides high tumoricidal depth (10 mm) for PDT of pancreatic cancer and should yield similar tumoricidal depth in CC. This study investigates the photodynamic characteristics of mTHPC in solvent-based formulation (Foscan (R)) and in liposomal (water soluble) formulation (Foslip (R)) in an in vitro model system consisting of two biliary cancer cell lines (GBC, gall bladder cancer and BDC, bile duct cancer cells). Dark toxicity, photodynamic efficiency, time-dependent uptake and retention and intracellular localization of Foscan (R) and Foslip (R) were studied. The results prove mTHPC as a potent photosensitizing agent with high phototoxic potential in biliary cancer cells as a concentration of 600 ng ml(-1) and irradiation with 1.5 J cm(-2) (660 +/- 10 nm) is sufficient for about 90% cell killing. Addition of foetal bovine serum (FBS) to the incubation medium and analysis of the uptake and phototoxic properties reveals that both photosensitizer formulations bind to serum protein fractions, i.e. no difference between Foscan (R) and Foslip (R) can be found in the presence of FBS. Laser scanning fluorescence microscopy indicates a similar pattern of perinuclear localization of both sensitizers. This study demonstrates the potential of mTHPC for treatment of bile duct malignancies and provides evidence that Foslip (R) is an equivalent water-soluble formulation of mTHPC that should ease intravenous application and thus clinical use of mTHPC.