Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates

被引:85
作者
SchmidtErfurth, U [1 ]
Diddens, H [1 ]
Birngruber, R [1 ]
Hasan, T [1 ]
机构
[1] HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114
关键词
photochemistry; ocular; neovascularization; chlorin;
D O I
10.1038/bjc.1997.9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Combination of photosensitizers with carrier molecules has been shown to enhance the efficiency of photodynamic therapy (PDT). Owing to an increased expression of their receptors on some malignant and proliferating cells, low-density lipoproteins (LDLs) are potential endogenous carriers. A photosensitizer, chlorin e(6) (Ce-6), was covalently bound to LDL via carbodiimide activation. The Ce-6-LDL conjugate was evaluated on a fibroblast cell line with defined LDL receptor expression and a retinoblastoma cell line (Y79). Uptake of free Ce-6 and Ce-6 either covalently bound to or complexed with LDL was measured by spectrofluorimetry. Phototoxicity after irradiation at 660 nm was determined by a mitochondrial activity assay (MTT). Covalent binding to LDL significantly increased the uptake of Ce, for both cell lines by a factor of 4-5. A Ce-6:LDL binding ratio of 50:1 was optimal. A receptor-mediated uptake was demonstrated by saturability and competitive inhibition by free LDL. Binding also occurred at 2 degrees C and was attributed to non-specific associations. Irradiation with 10 J cm(-2) of 660 nm light after treatment of cells with Ce-6-LDL conjugate reduced the MTT activity by 80%, while free or mixed Ce-6 induced a maximum of 10% reduction in the MTT activity following identical treatment conditions. These data suggest that targeting of LDL receptor-bearing cells using covalently bound carriers, such as LDL, might increase the efficiency and selectivity of PDT. Intraocular tumours such as retinoblastomas could be appropriate targets for such an approach owing to the ease of access of light sources and the need for non-invasive approaches in sensitive ocular sites.
引用
收藏
页码:54 / 61
页数:8
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