Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma
Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma
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DOI：
10.1016/j.pdpdt.2011.04.003
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发表时间：
2011-12-01
影响因子：
3.3
通讯作者：
Krammer, Barbara
中科院分区：
文献类型：
--
作者：
Sanovic, Renata;Verwanger, Thomas;Krammer, Barbara
背景：光动力疗法(PDT)在体内能否成功根除肿瘤取决于治疗参数的最佳组合。(低剂量)PDT还可以诱导抗肿瘤免疫反应。由于自然产生的金丝桃素(Hyp)是一种很有前途的光敏剂，本研究的目的是观察小剂量Hyp-PDT对小鼠肿瘤的光毒性和免疫学效应，并与常用的Hyp-PDT条件进行比较。方法：荷CT26结肠癌的Balb/c小鼠静脉注射金丝桃素，0.5-4h后接受红光照射。记录肿瘤生长情况。结果：根据不同的治疗方案，获得了不同的肿瘤/宿主反应结果，从小鼠因肿瘤生长延迟而退出到肿瘤完全消退。与对照组相比，普通剂量的PDT和4h的药物照射间隔导致肿瘤生长延迟4倍。PDT剂量较低，照射时间为0.5h，肿瘤消失率为100%。结论：药物浓度和光剂量似乎不仅决定了肿瘤的清除效率，而且决定了金丝桃素在照射时的定位。在我们的低剂量光动力疗法中，靶点完全是血管。这种低剂量的光动力疗法除了减少药物和动物的光照外，还具有减少皮肤损伤、加快损伤愈合和诱导抗肿瘤免疫反应的优点。(C)2011爱思唯尔B.V.保留所有权利。
Background: Successful tumor eradication with photodynamic therapy (PDT) in vivo depends on the optimal combination of treatment parameters. (Low-dose) PDT may additionally induce antitumoral immune responses. Since the naturally occurring hypericin (Hyp) is a promising photosensitizer for PDT, the aim of the study was to investigate phototoxic and immunologic effects of a low-dose Hyp-PDT on murine tumors in contrast to commonly used Hyp-PDT conditions.Methods: BALB/c mice bearing CT26 colon carcinoma received hypericin intravenously and were irradiated with red light 0.5-4h later. Tumor development was recorded. Mice were then re-challenged 60 days after the first tumor cell inoculation to investigate an antitumoral immune response.Results: Different results of tumor/host responses were obtained, ranging from mice exitus over delayed tumor growth to complete tumor regression according to different treatment protocols. PDT with common doses and a 4 h drug-light-interval resulted in a four times delayed tumor growth compared to the control groups. PDT with relatively low doses and a drug-light-interval of 0.5h led to 100% tumor eradication. Re-challenge of these mice with CT26 mouse colon carcinoma cells prevented new tumor growth.Conclusions: Not only drug concentrations and light doses seem to determine the efficiency of tumor eradication, but also the localization of hypericin at the time of irradiation. Targets in our low-dose PDT protocol are exclusively the vessels. The advantage of this low-dose PDT beside less drug and light exposure of the animals is reduced skin damage, faster healing of the lesions and induction of an antitumoral immune response. (C) 2011 Elsevier B.V. All rights reserved.