ACS Publications. Most Trusted. Most Cited. Most Read
A Cancer Cell Selective Replication Stress Nano Amplifier Promotes Replication Fork Catastrophe to Overcome Radioresistance

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Nano 2023, 17, 18, 18548-18561
    Article

    A Cancer Cell Selective Replication Stress Nano Amplifier Promotes Replication Fork Catastrophe to Overcome Radioresistance
    Click to copy article linkArticle link copied!

    • Hongwei Liao
      Hongwei Liao
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Hongwei Liao
    • Shengfei Yang
      Shengfei Yang
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Shengfei Yang
    • Zeyu Liang
      Zeyu Liang
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
      More by Zeyu Liang
    • Lin Xiao
      Lin Xiao
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Lin Xiao
    • Shangzhi Xie
      Shangzhi Xie
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Shangzhi Xie
    • Peihua Lin
      Peihua Lin
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Peihua Lin
    • Fan Xia
      Fan Xia
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Fan Xia
      Orcidhttps://orcid.org/0000-0002-2506-2051
    • Chunyan Fang
      Chunyan Fang
      Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
      More by Chunyan Fang
    • Qian Chen
      Qian Chen
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Qian Chen
    • Daishun Ling*
      Daishun Ling
      Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
      WLA Laboratories, Shanghai 201203, China
      *Email: [email protected]
      More by Daishun Ling
      Orcidhttps://orcid.org/0000-0002-9977-0237
    • Fangyuan Li*
      Fangyuan Li
      Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      WLA Laboratories, Shanghai 201203, China
      *Email: [email protected]
      More by Fangyuan Li
      Orcidhttps://orcid.org/0000-0002-8086-7362
    Other Access OptionsSupporting Information (1)

    ACS Nano

    Cite this: ACS Nano 2023, 17, 18, 18548–18561
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.3c06774
    Published September 14, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Replication stress (RS) induced by DNA damage plays a significant role in conferring the anticancer effects of radiotherapy and is tightly associated with radioresistance of cancer cells. Amplification of RS represents an effective approach to improving the efficacy of radiotherapy, although the development of selective RS amplifiers remains an unexplored frontier. We herein present an RS nano amplifier (RSNA) consisting of a catalytic FePt nanoparticle loaded with the chemotherapeutic doxorubicin (DOX), which selectively exacerbates RS in cancer cells by promoting replication fork (RF) catastrophe. RSNA converts the excessive reactive oxygen species (ROS) in cancer cells into oxygen, enhancing the DNA-damaging effects of radiotherapy to create more template lesions that impede RF progression in coalition with DOX. After radiation, ROS scavenging by RSNA accelerates RF progression through damaged template strands, increasing the frequency of RF collapse into double-strand breaks. Moreover, pretreatment with RSNA accumulates cancer cells in the S phase, exposing more RFs to radiation-induced RS. These effects of RSNA convergently maximize RS in cancer cells, effectively overcoming the radioresistance of cancer cells without affecting normal cells. Our study demonstrates the feasibility of selectively amplifying RS to boost radiotherapy.

    Copyright © 2023 American Chemical Society

    Subjects

    what are subjects

    Keywords

    what are keywords

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.3c06774.

    • Additional results for nanoparticle TEM image, size distribution, XPS spectrum, colloidalstability, Zeta potentials, drug loading efficiency assays, drug release assays, catalytic activities assays, MR imaging performance assays, cellular internalization analysis, γH2AX immunofluorescence analysis, DCF immunofluorescence analysis, cell viability assays, H&E-stained images of organs, MRI and H&E staining of the rectum region of tumor-bearing mice (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 6 publications.

    1. Dongmei Yang, Minjia Yuan, Jianbo Huang, Xi Xiang, Houqing Pang, Qiang Wei, Xianglin Luo, Chong Cheng, Li Qiu, Lang Ma. Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis. ACS Nano 2024, 18 (4) , 3424-3437. https://doi.org/10.1021/acsnano.3c10552
    2. Yujia Liang, Shufang Ning, Mekhrdod S. Kurboniyon, Khaiyom Rahmonov, Zhengmin Cai, Shirong Li, Jinling Mai, Xiaojing He, Lijuan Liu, Liping Tang, Litu Zhang, Chen Wang. PdRu bimetallic nanoalloys with improved photothermal effect for amplified ROS-mediated tumor therapy. Frontiers in Bioengineering and Biotechnology 2025, 12 https://doi.org/10.3389/fbioe.2024.1523599
    3. Jipeng Yao, Zhencun Cui, Feifei Zhang, Haidong Li, Longlong Tian. Biomaterials enhancing localized cancer therapy activated anti-tumor immunity: a review. Journal of Materials Chemistry B 2024, 13 (1) , 117-136. https://doi.org/10.1039/D4TB01995D
    4. Hao Xu, Jin Xing, Lilin Cheng, Zhihan Wang, Liang Zhao, Li Ren, Shuai Zhang. CircFOXO3 upregulation mediates the radioresistance of glioblastoma by affecting cellular metabolome. Frontiers in Pharmacology 2024, 15 https://doi.org/10.3389/fphar.2024.1479480
    5. Minqian Zhu, Yuanyuan Ren, Hailin Zhou, Li Guo, Hengyu Zhang, Tao Yang, Xuan Yi. Differential regulation of radio-sensitivity/macrophage polarization in intestinal tissue and colorectal cancer for the optimized preoperative radiotherapy. Chemical Engineering Journal 2024, 498 , 155211. https://doi.org/10.1016/j.cej.2024.155211
    6. Yani Zou, Helin Xu, Xiu Wu, Xuesong Liu, Jianfu Zhao. Enhancing Radiotherapy Sensitivity in Prostate Cancer with Lentinan-Functionalized Selenium Nanoparticles: Mechanistic Insights and Therapeutic Potential. Pharmaceutics 2024, 16 (9) , 1230. https://doi.org/10.3390/pharmaceutics16091230
    7. Hao Xu, Jin Xing, Linlin Cheng, Zhihan wang, Liang zhao, Li Ren, Shuai Zhang. CircFOXO3 Upregulation Mediates the Radioresistance of Glioblastoma by Affecting Cellular Metabolome. 2023https://doi.org/10.21203/rs.3.rs-3474740/v1
    Download PDF
    Go to ACS Nano
    Get e-Alerts
    Get e-Alerts

    ACS Nano

    Cite this: ACS Nano 2023, 17, 18, 18548–18561
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.3c06774
    Published September 14, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

    Article Views

    1234

    Altmetric

    -

    Citations

    6
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.