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作者

Haijun Wang Xichen Zhao Heng Zhang Xianwen Zou Dianlong Jia Wenjian Liu Baoqing Tian Dandan Yuan Yihui Li Yao Zhu Fan Zhang Yongsi Dai Yu Fan Yuchun Wei Xiao Sun Qing Fan Jian Dong

作者单位

⁶Laboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng University, Liaocheng, 252000, China ¹Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, 250117, China ⁷Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074, Aachen, Germany ³These authors have contributed equally to this work. ⁵School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, 271016, China ²School of Life Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, 271016, China ⁴Department of Oncology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, 271000, China

刊名

Materials Today Advances

年份

2023

卷号

Vol.18

页码

100375

ISSN

2590-0498

关键词

Platinum nanozyme Polydopamine Affibody EGFR Radiosensitization

摘要

Clinical radiotherapy is severely limited by hypoxic tumor microenvironment and a lack of targeting precision. Therefore, it is crucial to develop highly efficient radiosensitizers to enhance RT efficacy. Herein, a novel kind of epidermal growth factor receptor -antagonistic affibody-functionalized Pt-based nanozyme for RT sensitization to EGFR-positive tumors was developed. In this study, porous platinum nanoparticles featuring catalase -like activity and strong radiation energy absorption ab...更多

Clinical radiotherapy is severely limited by hypoxic tumor microenvironment and a lack of targeting precision. Therefore, it is crucial to develop highly efficient radiosensitizers to enhance RT efficacy. Herein, a novel kind of epidermal growth factor receptor -antagonistic affibody-functionalized Pt-based nanozyme for RT sensitization to EGFR-positive tumors was developed. In this study, porous platinum nanoparticles featuring catalase -like activity and strong radiation energy absorption ability were first synthesized. Then, a thin biomimetic polydopamine layer was coated on pPt NPs to optimize its biocompatibility as well as provide a reactive surface. Finally, a dimeric EGFR-antagonistic affibody called Z expressed by the Escherichia coli , was conjugated to pPt@PDA NPs to precisely recognize EGFR-positive A431 tumors. Under the navigation of Z, superior tumor homing was achieved with these Pt-based nanozymes, which was ascribed to EGFR receptor-mediated endocytosis. As high-Z metal NPs exhibit an inherently strong ability to absorb radiation energy and catalyze endogenous HO in tumors, the pPt@PDA-Z NPs demonstrated superb therapeutic efficacy; specifically, the NPs significantly inhibited HIF-1α expression and increased RT-induced DNA damage. Furthermore, the biosafety of these Pt-based nanozymes was good during short-term treatment. In summary, EGFR-antagonistic affibody-functionalized Pt-based nanozymes are promising radiosensitizers for the precise therapy of EGFR-positive tumors.收起

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