IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47080-3.html
   My bibliography  Save this article

Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer

Author

Listed:
  • Yu-Yang Bi

    (China Pharmaceutical University)

  • Qiu Chen

    (China Pharmaceutical University)

  • Ming-Yuan Yang

    (China Pharmaceutical University)

  • Lei Xing

    (China Pharmaceutical University
    China Pharmaceutical University)

  • Hu-Lin Jiang

    (China Pharmaceutical University
    China Pharmaceutical University
    Yanbian University)

Abstract

Non-small cell lung cancer (NSCLC) shows high drug resistance and leads to low survival due to the high level of mutated Tumor Protein p53 (TP53). Cisplatin is a first-line treatment option for NSCLC, and the p53 mutation is a major factor in chemoresistance. We demonstrate that cisplatin chemotherapy increases the risk of TP53 mutations, further contributing to cisplatin resistance. Encouragingly, we find that the combination of cisplatin and fluvastatin can alleviate this problem. Therefore, we synthesize Fluplatin, a prodrug consisting of cisplatin and fluvastatin. Then, Fluplatin self-assembles and is further encapsulated with poly-(ethylene glycol)–phosphoethanolamine (PEG–PE), we obtain Fluplatin@PEG–PE nanoparticles (FP NPs). FP NPs can degrade mutant p53 (mutp53) and efficiently trigger endoplasmic reticulum stress (ERS). In this study, we show that FP NPs relieve the inhibition of cisplatin chemotherapy caused by mutp53, exhibiting highly effective tumor suppression and improving the poor NSCLC prognosis.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47080-3
    DOI: 10.1038/s41467-024-47080-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47080-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-47080-3?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. JianGen Gong & Antonio Costanzo & Hong-Qiong Yang & Gerry Melino & William G. Kaelin & Massimo Levrero & Jean Y. J. Wang, 1999. "The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage," Nature, Nature, vol. 399(6738), pages 806-809, June.
    2. Sohrab Salehi & Farhia Kabeer & Nicholas Ceglia & Mirela Andronescu & Marc J. Williams & Kieran R. Campbell & Tehmina Masud & Beixi Wang & Justina Biele & Jazmine Brimhall & David Gee & Hakwoo Lee & J, 2021. "Clonal fitness inferred from time-series modelling of single-cell cancer genomes," Nature, Nature, vol. 595(7868), pages 585-590, July.
    3. Roy S. Herbst & Daniel Morgensztern & Chris Boshoff, 2018. "The biology and management of non-small cell lung cancer," Nature, Nature, vol. 553(7689), pages 446-454, January.
    4. Timour Baslan & John P. Morris & Zhen Zhao & Jose Reyes & Yu-Jui Ho & Kaloyan M. Tsanov & Jonathan Bermeo & Sha Tian & Sean Zhang & Gokce Askan & Aslihan Yavas & Nicolas Lecomte & Amanda Erakky & Anna, 2022. "Ordered and deterministic cancer genome evolution after p53 loss," Nature, Nature, vol. 608(7924), pages 795-802, August.
    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. Xiaobo Yang & Zhilong Mi & Qingcai He & Binghui Guo & Zhiming Zheng, 2023. "Identification of Vital Genes for NSCLC Integrating Mutual Information and Synergy," Mathematics, MDPI, vol. 11(6), pages 1-15, March.
    2. Xiang Ge Luo & Jack Kuipers & Niko Beerenwinkel, 2023. "Joint inference of exclusivity patterns and recurrent trajectories from tumor mutation trees," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Hongyu Shi & Marc J. Williams & Gryte Satas & Adam C. Weiner & Andrew McPherson & Sohrab P. Shah, 2024. "Allele-specific transcriptional effects of subclonal copy number alterations enable genotype-phenotype mapping in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Mei Zhao & Tianxiao Wang & Frederico O. Gleber-Netto & Zhen Chen & Daniel J. McGrail & Javier A. Gomez & Wutong Ju & Mayur A. Gadhikar & Wencai Ma & Li Shen & Qi Wang & Ximing Tang & Sen Pathak & Mari, 2024. "Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Michael J. P. Crowley & Bhavneet Bhinder & Geoffrey J. Markowitz & Mitchell Martin & Akanksha Verma & Tito A. Sandoval & Chang-Suk Chae & Shira Yomtoubian & Yang Hu & Sahil Chopra & Diamile A. Tavarez, 2023. "Tumor-intrinsic IRE1α signaling controls protective immunity in lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Feras E. Machour & Enas R. Abu-Zhayia & Joyce Kamar & Alma Sophia Barisaac & Itamar Simon & Nabieh Ayoub, 2024. "Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Wei Jiang & Qitao Yu, 2019. "LKB1, a Key Driver Gene of Human Lung Squamous Cell Carcinoma," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 19(3), pages 14335-14336, July.
    8. Meng Nie & Ke Yao & Xinsheng Zhu & Na Chen & Nan Xiao & Yi Wang & Bo Peng & LiAng Yao & Peng Li & Peng Zhang & Zeping Hu, 2021. "Evolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    9. Peter Bailey & Rachel A. Ridgway & Patrizia Cammareri & Mairi Treanor-Taylor & Ulla-Maja Bailey & Christina Schoenherr & Max Bone & Daniel Schreyer & Karin Purdie & Jason Thomson & William Rickaby & R, 2023. "Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Chen Ni & Xiaohan Lou & Xiaohan Yao & Linlin Wang & Jiajia Wan & Xixi Duan & Jialu Liang & Kaili Zhang & Yuanyuan Yang & Li Zhang & Chanjun Sun & Zhenzhen Li & Ming Wang & Linyu Zhu & Dekang Lv & Zhih, 2022. "ZIP1+ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn2+ transfer," Nature Communications, Nature, vol. 13(1), pages 1-20, 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:15:y:2024:i:1:d:10.1038_s41467-024-47080-3. 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.