An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy.
An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy.
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DOI：
10.1038/s41598-017-13803-4
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发表时间：
2017-10-17
影响因子：
4.6
通讯作者：
Evans CL
中科院分区：
文献类型：
--
作者：
Klein OJ;Yuan H;Nowell NH;Kaittanis C;Josephson L;Evans CL
靶向抗肿瘤药物在癌症治疗中显示出巨大的希望，它具有仅对特定肿瘤类型施加细胞毒性的能力。然而，这些疗法不能在整个肿瘤中均匀吸收，导致亚致死细胞死亡，从而导致治疗耐药性，并导致有问题的脱靶效应。在这里，我们展示了一种光动力治疗结构，它既整合了用于整合素靶向的环状RGD片段，也整合了一个5kda的PEG链，使该结构钝化并使其能够在肿瘤中快速扩散。研究发现，光敏剂结构的聚乙二醇化可以防止光敏剂聚集，促进细胞毒性活性自由基的产生，并使该结构能够快速被吸收到整个大（直径500µm） 3D肿瘤球体的细胞中。用一般的RAD肽代替环状RGD导致3D培养中细胞摄取的丧失，证明了该结构的特异性。该结构的光动力疗法成功地诱导了细胞毒性，这种毒性可以被10倍浓度的自由循环RGD竞争性地阻断。这种结构是同类疗法中的第一种，可以作为我们不断增长的治疗工具箱中的一种新方法。
Targeted antineoplastic agents show great promise in the treatment of cancer, having the ability to impart cytotoxicity only to specific tumor types. However, these therapies do not experience uniform uptake throughout tumors, leading to sub-lethal cell killing that can impart treatment resistance, and cause problematic off-target effects. Here we demonstrate a photodynamic therapy construct that integrates both a cyclic RGD moiety for integrin-targeting, as well as a 5 kDa PEG chain that passivates the construct and enables its rapid diffusion throughout tumors. PEGylation of the photosensitizer construct was found to prevent photosensitizer aggregation, boost the generation of cytotoxic reactive radical species, and enable the rapid uptake of the construct into cells throughout large (>500 µm diameter) 3D tumor spheroids. Replacing the cyclic RGD with the generic RAD peptide led to the loss of cellular uptake in 3D culture, demonstrating the specificity of the construct. Photodynamic therapy with the construct was successful in inducing cytotoxicity, which could be competitively blocked by a tenfold concentration of free cyclic RGD. This construct is a first-of-its kind theranostic that may serve as a new approach in our growing therapeutic toolbox.
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影响因子：
4.7
作者：
Ito K;Mitsunaga M;Nishimura T;Saruta M;Iwamoto T;Kobayashi H;Tajiri H
通讯作者：
Tajiri H
氯素E6通过干细胞运输的有效光动力疗法运输的功能化疗法多阶段纳米腔。
影响因子：
9.5
作者：
Näkki S;Martinez JO;Evangelopoulos M;Xu W;Lehto VP;Tasciotti E
通讯作者：
Tasciotti E
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
影响因子：
3.8
作者：
Evans, Conor L.;Rizvi, Imran;de Boer, Johannes F.
通讯作者：
de Boer, Johannes F.
影响因子：
3.7
作者：
Chen XL;Lei YH;Liu CF;Yang QF;Zuo PY;Liu CY;Chen CZ;Liu YW
通讯作者：
Liu YW