Elucidation of the tumoritropic principle of hypericin

被引:42
作者
Van de Putte, M
Roskams, T
Vandenheede, JR
Agostinis, P
de Witte, PAM
机构
[1] Katholieke Univ Leuven, Fac Farmaceut Wetenschappen, Lab Farmaceut Biol, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Fac Geneeskunde, Afdeling Histochem & Cytochem, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, Fac Geneeskunde, Afdeling Biochem, B-3000 Louvain, Belgium
关键词
photodynamic therapy; hypericin; tumoritropic behaviour; perfusion; permeability; lipoproteins;
D O I
10.1038/sj.bjc.6602512
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hypericin is a potent agent in the photodynamic therapy of cancers. To better understand its tumoritropic behaviour, we evaluated the major determinants of the accumulation and dispersion of hypericin in subcutaneously growing mouse tumours. A rapid exponential decay in tumour accumulation of hypericin as a function of tumour weight was observed for each of the six tumour models investigated, and a similar relationship was found between tumour blood flow and tumour weight. Moreover, there was a close correlation between the higher hypericin uptake in RIF-1 tumours compared to R1 tumours and tumour vessel permeability. To define the role of lipoproteins in the transport of hypericin through the interstitial space, we performed a visual and quantitative analysis of the colocalisation of hypericin and DiOC(18)-labelled lipoproteins in microscopic fluorescent overlay images. A coupled dynamic behaviour was found early after injection ( normalised fluorescence intensity differences were on the whole less than 10%), while a shifted pattern in localisation of hypericin and DiOC(18) was seen after 24 h, suggesting that during its migration through the tumour mass, hypericin is released from the lipoprotein complex. In conclusion, we were able to show that the tumour accumulation of hypericin is critically determined by a combination of biological ( blood flow, vessel permeability) and physicochemical elements ( affinity for interstitial constituents).
引用
收藏
页码:1406 / 1413
页数:8
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