Supramolecular Nanofibers of Curcumin for Highly Amplified Radiosensitization of Colorectal Cancers to Ionizing Radiation
Supramolecular Nanofibers of Curcumin for Highly Amplified Radiosensitization of Colorectal Cancers to Ionizing Radiation
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姜黄素超分子纳米纤维对结直肠癌电离辐射的高放大放射增敏作用
DOI：
10.1002/adfm.201707140
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发表时间：
2018-04-05
影响因子：
19
通讯作者：
Ding, Dan
中科院分区：
文献类型：
--
作者：
Xu, Huae;Wang, Tingting;Ding, Dan
开发高效的放射增敏剂是解决癌细胞对电离辐射抵抗的迫切需要，这是放疗失败的主要原因。本文首次报道了超分子纳米材料可以作为开发高性能放射增敏剂的优良纳米平台。一种基于姜黄素自组装短肽的超分子纳米纤维（Cur - SNF）被开发出来，极大地提高了结直肠癌对电离辐射的辐射敏感性。合成了药物-肽缀合物Curcumin - FFE - CS - EE，并可自组装成由还原剂触发的含有Cur - snf的小分子水凝胶。体外和体内的放射增敏研究表明，与游离姜黄素相比，由于其超分子纳米结构，Cur‐snf作为一种放射增敏剂，在使结直肠癌细胞对电离辐射增敏方面表现得更好。由于异常高的放射增敏效果，Cur‐SNFs联合放疗可显著减少体内肿瘤体积。此外，分子机制研究表明，Cur‐SNFs通过抑制辐射诱导的核因子κ B激活来促进结直肠癌细胞的放射敏感性。Cur‐SNF在10%细胞存活值2.01时实现了超大的增敏剂增强比，是目前报道的基于姜黄素的放射增敏剂中最高的。
Development of highly efficient radiosensitizers is urgently desirable for addressing the resistance of cancer cells to ionizing radiation, which is the main reason for the failure of radiotherapy. Here, it is reported for the first time that supramolecular nanomaterials can serve as an excellent nanoplatform for developing superior radiosensitizers. A new curcumin‐based supramolecular nanofiber (Cur‐SNF) by virtue of a self‐assembling short peptide is developed, which greatly boosts the radiosensitivity of colorectal cancers to ionizing radiation. The drug–peptide conjugate Curcumin‐FFE‐CS‐EE is synthesized and can self‐assemble into small‐molecule hydrogel containing Cur‐SNFs triggered by reductant. In vitro and in vivo radiosensitization studies reveal that as compared to free curcumin Cur‐SNFs show much better performance as a radiosensitizer to sensitize colorectal cancer cells to ionizing radiation thanks to the supramolecular nanostructure. Due to the exceptionally high radiosensitization efficacy, Cur‐SNFs in combination with radiation realize significant reduction in tumor volume in vivo. Besides, the molecular mechanism studies demonstrate that Cur‐SNFs promote the radiosensitivity of colorectal cancer cells through inhibiting radiation‐induced nuclear factor kappa B activation. Cur‐SNF achieves an ultralarge sensitizer enhancement ratio at 10% cell survival value of 2.01, the highest among currently reported curcumin‐based radiosensitizers.