IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60798-y.html
   My bibliography  Save this article

Dual asparagine-depriving nanoparticles against solid tumors

Author

Listed:
  • Yubo Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Huifang Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Daoxia Guo

    (Shanghai Jiao Tong University School of Medicine)

  • Jiantao Liu

    (Shanghai Normal University)

  • Jinli Sun

    (Shanghai Jiao Tong University School of Medicine)

  • Nan Chen

    (Shanghai Normal University)

  • Haiyun Song

    (Shanghai Jiao Tong University School of Medicine)

  • Xiaoyuan Ji

    (Shanghai Jiao Tong University School of Medicine)

Abstract

Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia, whereas solid tumors are unresponsive to this therapy owing to their active Asn biosynthesis. Herein, we develop a type of core-shell structured cascade-responsive nanoparticles (NPs) for sequential modulation of exogenous Asn supply and endogenous Asn production. The reactive oxygen species-sensitive NP shells disintegrate in the tumor microenvironment and liberate ASNase to scavenge extracellular Asn. The acid-labile NP cores subsequently decompose in the tumor cells and release rotenone to block intracellular Asn biosynthesis. Administration of the dual Asn-depriving NPs in murine models of triple-negative breast cancer and colorectal cancer substantially suppress the growth and epithelial-mesenchymal transition of primary and relapsed tumors, fully eradicate spontaneous and post-surgical metastasis, and confer long-term T cell memory for complete resistance to tumor rechallenge. This study represents a generalized strategy to harness amino acid depletion therapy against solid tumors.

Suggested Citation

  • Yubo Shen & Huifang Wang & Daoxia Guo & Jiantao Liu & Jinli Sun & Nan Chen & Haiyun Song & Xiaoyuan Ji, 2025. "Dual asparagine-depriving nanoparticles against solid tumors," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60798-y
    DOI: 10.1038/s41467-025-60798-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60798-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60798-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Minjun Xu & Kaili Hu & Yipu Liu & Yukun Huang & Shanshan Liu & Yu Chen & Dayuan Wang & Songlei Zhou & Qian Zhang & Ni Mei & Huiping Lu & Fengan Li & Xiaoling Gao & Jun Chen, 2021. "Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Justine Lengrand & Ievgenia Pastushenko & Sebastiaan Vanuytven & Yura Song & David Venet & Rahul M. Sarate & Melanie Bellina & Virginie Moers & Alice Boinet & Alejandro Sifrim & Nicolas Rama & Benjami, 2023. "Pharmacological targeting of netrin-1 inhibits EMT in cancer," Nature, Nature, vol. 620(7973), pages 402-408, August.
    3. Abigail S. Krall & Shili Xu & Thomas G. Graeber & Daniel Braas & Heather R. Christofk, 2016. "Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    4. Luis Felipe Campesato & Sadna Budhu & Jeremy Tchaicha & Chien-Huan Weng & Mathieu Gigoux & Ivan Jose Cohen & David Redmond & Levi Mangarin & Stephane Pourpe & Cailian Liu & Roberta Zappasodi & Dmitriy, 2020. "Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    5. Urbain Weyemi & Christophe E. Redon & Rohini Choudhuri & Towqir Aziz & Daisuke Maeda & Myriem Boufraqech & Palak R. Parekh & Taresh K. Sethi & Manjula Kasoji & Natalie Abrams & Anand Merchant & Vinodh, 2016. "The histone variant H2A.X is a regulator of the epithelial–mesenchymal transition," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    6. Xin Guan & Liping Sun & Yuting Shen & Fengshan Jin & Xiaowan Bo & Chunyan Zhu & Xiaoxia Han & Xiaolong Li & Yu Chen & Huixiong Xu & Wenwen Yue, 2022. "Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Yu-Yang Bi & Qiu Chen & Ming-Yuan Yang & Lei Xing & Hu-Lin Jiang, 2024. "Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Julie Talbot & Joanna Fombonne & Jacob Torrejon & Benjamin R. Babcock & Leon F. McSwain & Nicolas Rama & Ludovica Lospinoso Severini & Emma Bonerandi & Veronique Marsaud & Flavia Bernardi & Tarek Ghar, 2025. "Sonic hedgehog medulloblastomas are dependent on Netrin-1 for survival," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    2. Shuiling Chen & Yang Luo & Yang He & Ming Li & Yongjian Liu & Xishen Zhou & Jianwen Hou & Shaobing Zhou, 2024. "In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Tianyu Tang & Xing Huang & Minghao Lu & Gang Zhang & Xu Han & Tingbo Liang, 2023. "Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Qiming Zhou & Yao Peng & Fenfen Ji & Huarong Chen & Wei Kang & Lam-Shing Chan & Hongyan Gou & Yufeng Lin & Pingmei Huang & Danyu Chen & Qinyao Wei & Hao Su & Cong Liang & Xiang Zhang & Jun Yu & Chi Ch, 2023. "Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Yuechen Liu & Zhengyu Liu & Yating Hu & Yunyan Ling & Shunjie Qing & Yang Liu & Yizhi Zhan & Zhiyong Shen & Yuan Fang & Haijun Deng, 2025. "Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    6. Rens Peeters & Jorge Cuenca-Escalona & Esther A. Zaal & Anna T. Hoekstra & Anouk C. G. Balvert & Marcos Vidal-Manrique & Niek Blomberg & Sjoerd J. Deventer & Rinke Stienstra & Julia Jellusova & Martin, 2022. "Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Enni Chen & Jiawei Wu & Jiajia Huang & Wancui Zhu & Haohui Sun & Xiaonan Wang & Dagui Lin & Xiaodi Li & Dingbo Shi & Zhiqiao Liu & Jinsheng Huang & Miao Chen & Fangyun Xie & Wuguo Deng, 2024. "FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Haoyue Xue & Jing Jin & Xing Huang & Zhi Tan & Yushun Zeng & Gengxi Lu & Xin Hu & Keliang Chen & Yonglin Su & Xiaolin Hu & Xingchen Peng & Laiming Jiang & Jiagang Wu, 2025. "Wearable flexible ultrasound microneedle patch for cancer immunotherapy," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    9. Celia D. Rouault & Lucile Bansard & Elena Martínez-Balsalobre & Caroline Bonnet & Julien Wicinski & Shuheng Lin & Ludovic Colombeau & Sylvain Debieu & Guillaume Pinna & Marie Vandamme & Margot Machu &, 2025. "Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    10. Shuyan Dai & Lingzhi Qu & Jun Li & Ye Zhang & Longying Jiang & Hudie Wei & Ming Guo & Xiaojuan Chen & Yongheng Chen, 2022. "Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Songlei Zhou & Yukun Huang & Yu Chen & Yipu Liu & Laozhi Xie & Yang You & Shiqiang Tong & Jianpei Xu & Gan Jiang & Qingxiang Song & Ni Mei & Fenfen Ma & Xiaoling Gao & Hongzhuan Chen & Jun Chen, 2023. "Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    12. Bo Wang & Jing Chen & Julia S. Caserto & Xi Wang & Minglin Ma, 2022. "An in situ hydrogel-mediated chemo-immunometabolic cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60798-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.