Far-red light activatable, multifunctional prodrug for fluorescence optical imaging and combinational treatment.

Far-red light activatable, multifunctional prodrug for fluorescence optical imaging and combinational treatment.
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远红色的光线可激活,多功能前药,用于荧光光学成像和组合处理。

DOI:
10.1021/jm5000722
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发表时间:
2014-04-24
影响因子:
7.3
通讯作者:
You Y
You Y
中科院分区:
医学1区
文献类型:
--
作者:
Bio M;Rajaputra P;Nkepang G;You Y

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我们最近开发了一种新的化学工具“光解键化学”,涉及单线态氧对氨基丙烯酸酯的裂解,并展示了其在可见光活化前药中的应用。本研究制备了一种先进的多功能前药Pc-(L-CA4)2,由荧光光敏剂酞菁(Pc)、so不稳定的氨基丙烯酸酯连接剂(L)和细胞毒性药物combretastatin a -4 (CA4)组成。与CA4相比,Pc-(L-CA4)2具有较低的暗毒性。然而,一旦被照亮,它表现出与CA4相似的改善毒性,并在体外表现出旁观者效应。我们利用活体小鼠的光学成像技术监测了Pc-(L-CA4)2的时间依赖性分布。我们还通过光动力治疗(PDT)和释放化疗药物的联合作用,对小鼠进行远红光照射,有效地消融肿瘤,无任何急性全身毒性迹象。
We recently developed “photo-unclick chemistry”, a novel chemical tool involving the cleavage of aminoacrylate by singlet oxygen, and demonstrated its application to visible light-activatable prodrugs. In this study, we prepared an advanced multifunctional prodrug, Pc-(L-CA4)2, composed of the fluorescent photosensitizer phthalocyanine (Pc), an SO-labile aminoacrylate linker (L), and a cytotoxic drug combretastatin A-4 (CA4). Pc-(L-CA4)2 had reduced dark toxicity compared with CA4. However, once illuminated, it showed improved toxicity similar to CA4 and displayed bystander effects in vitro. We monitored the time-dependent distribution of Pc-(L-CA4)2 using optical imaging with live mice. We also effectively ablated tumors by the illumination with far-red light to the mice, presumably through the combined effects of photodynamic therapy (PDT) and released chemotherapy drug, without any sign of acute systemic toxicity.
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