Selective antitumor effect of novel protease-mediated photodynamic agent
Selective antitumor effect of novel protease-mediated photodynamic agent
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DOI：
10.1158/0008-5472.can-06-0448
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发表时间：
2006-07-15
期刊：
影响因子：
11.2
通讯作者：
Tung, Ching-Hsuan
中科院分区：
文献类型：
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作者：
Choi, Yongdoo;Weissleder, Ralph;Tung, Ching-Hsuan
通过设计对肿瘤相关蛋白酶敏感的含氯e6 （Ce6）大分子，开发了一种选择性光动力治疗（PDT）的新方法。这些试剂在天然状态下是无毒的，但在蛋白酶转化时变成荧光并产生单线态氧。结合优化的给药系统，我们发现(a)由于增强的渗透性和滞留效应，药物有效地在肿瘤中积累，(b)药物被蛋白酶局部激活，(c)局部药物浓度，可以通过定量荧光断层扫描测量，(d)光处理的肿瘤显示出生长减少。单次低剂量PDT （0.125 mg Ce6当量/kg）足以抑制肿瘤生长50%。可活化的单线态产氧剂具有更高的效能和更低的毒性，可能成为一种强大的PDT。
A new approach to selective photodynamic therapy (PDT) was developed by designing chlorin e6 (Ce6)-containing macromolecules, which are sensitive to tumor-associated proteases. The agents are nontoxic in their native state but become fluorescent and produce singlet oxygen on protease conversion. Coupled with optimized delivery svstems, we show that (a) the agents efficiently accumulate in tumors due to the enhanced permeability and retention effect, (b) the agents are locally activated by proteases, (c) local drug concentration,, can be measured by quantitative fluorescence tomography, and (d) light-treated tumors show reduced growth. A single low dose of PDT (0.125 mg Ce6 equivalent/kg) was sufficient to suppress tumor growth by > 50%. Activatable singlet oxygen generation agents provide increased efficacy with reduced toxicity, and it could become a powerful PDT.