IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-64212-5.html
   My bibliography  Save this article

Virus-inspired lipopeptide-derived nucleic acid delivery to cartilage for osteoarthritis therapy

Author

Listed:
  • Yu Fu

    (Southwest University)

  • Yulan Huang

    (Southwest University
    Chongqing University of Technology
    Fudan University)

  • Yunjiao Wang

    (Army Medical University (Third Military Medical University))

  • Zhenlan Fu

    (Army Medical University (Third Military Medical University))

  • Wenyun Cai

    (Southwest University
    Fudan University)

  • Lu Wang

    (Southwest University)

  • Yuchun Wu

    (Southwest University)

  • Xing Zhou

    (Chongqing University of Technology)

  • Zhongyi Ma

    (Southwest University)

  • Zhigang Xu

    (Southwest University)

  • Yaqin Tang

    (Chongqing University of Technology)

  • Jing Xie

    (Chongqing University of Technology)

  • Jiayun Jiang

    (Army Medical University (Third Military Medical University))

  • Robert J. Lee

    (The Ohio State University)

  • Chong Li

    (Southwest University
    Southern Medical University)

Abstract

Cartilage-targeted gene therapy is promising for osteoarthritis (OA) treatment, though its potency critically depends on the effectiveness of delivery vectors. Here, we modularly develop a series of non-pathogenic, virus-inspired lipopeptide-based nanoparticles (VPN) tailored to deliver nucleic acids to cartilage. The cationic moiety of lipopeptide with variable arginine and histidine residues is the key functional component, and screened by in vitro performance. The optimized VPN-2 with a moiety of –[(R)5-(H)4]2- facilitates sufficient endocytosis and effective lysosomal escape, achieving about 2.5-fold improvement in transfection potency over conventional lipid nanoparticles. To address the tradeoff between penetration and retention within articular cartilage, si-VPN-2 is further formulated into ROS-responsive nano-in-gel system, which turns out to alleviate cartilage degeneration in surgical ACTL mice, and further synergizes with methylprednisolone to implement superior joint protection in PTOA mice. Our study underscores the platform’s potential of VPN as cartilage-targeted RNA delivery vector for innovative OA therapy.

Suggested Citation

  • Yu Fu & Yulan Huang & Yunjiao Wang & Zhenlan Fu & Wenyun Cai & Lu Wang & Yuchun Wu & Xing Zhou & Zhongyi Ma & Zhigang Xu & Yaqin Tang & Jing Xie & Jiayun Jiang & Robert J. Lee & Chong Li, 2025. "Virus-inspired lipopeptide-derived nucleic acid delivery to cartilage for osteoarthritis therapy," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64212-5
    DOI: 10.1038/s41467-025-64212-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-64212-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-64212-5?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. Kaicheng Tang & Zhongjie Tang & Miaomiao Niu & Zuyin Kuang & Weiwei Xue & Xinyu Wang & Xinlong Liu & Yang Yu & Seongdong Jeong & Yifan Ma & Annette Wu & Betty Y. S. Kim & Wen Jiang & Zhaogang Yang & C, 2025. "Allosteric targeted drug delivery for enhanced blood-brain barrier penetration via mimicking transmembrane domain interactions," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Xufei Bian & Ling Yang & Dingxi Jiang & Adam J. Grippin & Yifan Ma & Shuang Wu & Linchong Wu & Xiaoyou Wang & Zhongjie Tang & Kaicheng Tang & Weidong Pan & Shiyan Dong & Betty Y. S. Kim & Wen Jiang & , 2024. "Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles," Nature Communications, Nature, vol. 15(1), pages 1-17, 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.

      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_s41467-025-64212-5. 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.