首页|Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

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The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled con-trol formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALP-high-expressing cancer cells to γ-rays,with a remarkable sensitizer enhancement ratio.Our results indi-cated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

In situ enzyme-instructed self-assembly(EISA)Pre-assemblyAlkaline phosphatase(AIP)PeptideCancer radiotherapyNanofiberHistone deacetylases inhibitor(HDACI)Radiosensitizer

Yang Gao、Jie Gao、Ganen Mu、Yumin Zhang、Fan Huang、Wenxue Zhang、Chunhua Ren、Cuihong Yang、Jianfeng Liu

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Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin 300192,China

Radiation Oncology Department,Tianjin Medical University General Hospital,Tianjin 300052,China

National Natural Science Foun-dation of ChinaNational Natural Science Foun-dation of ChinaNational Natural Science Foun-dation of ChinaCAMS Innovation Fund for Medical SciencesCAMS Innovation Fund for Medical SciencesCAMS Innovation Fund for Medical SciencesNon-profit Central Research Institute Fund of Chinese Academy of Medical SciencesNon-profit Central Research Institute Fund of Chinese Academy of Medical SciencesNon-profit Central Research Institute Fund of Chinese Academy of Medical Sciencesand the Science Foundation for Distin-guished Young Scholars of Tianjinand the Science Foundation for Distin-guished Young Scholars of Tianjinand the Science Foundation for Distin-guished Young Scholars of Tianjin

819717333177108581722026CIFMS2016-I2M-3-022China2018RC3500162018PT35031China18JCJQJC4730019JCJQJC62200China

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(12)
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