The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy

Xueyi Hu, Yichun Wang, Ruohan Wang, Yiyao Pu, Rongrong Jin (), Yu Nie () and Xintao Shuai
Additional contact information
Xueyi Hu: Sichuan University
Yichun Wang: Sichuan University
Ruohan Wang: Sichuan University
Yiyao Pu: Sichuan University
Rongrong Jin: Sichuan University
Yu Nie: Sichuan University
Xintao Shuai: The Third Affiliated Hospital of Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Delivering plasmid DNA (pDNA) to solid tumors remains a significant challenge due to the requirement for multiple transport steps and the need to promote delivery efficiency. Herein, we present a virus-mimicking hybrid lipoplex, composed of an arginine-rich cationic lipid, hyaluronic acid derivatives coated gold nanoparticles, and pDNA. This system induces cytoskeletal rearrangements through “outside-in” mechanical and “inside-out” biochemical signaling, overcoming intra- and intercellular barriers to enhance pDNA delivery. By modulating autophagy, RhoA signaling, and cytoskeletal dynamics, we achieve a 20-fold increase in gene expression with high tissue specificity in solid tumors. Furthermore, the system is applied to co-deliver a p53 plasmid and an MDM2 inhibitor, demonstrating significant synergistic antitumor effects in hepatocellular and lung carcinomas.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55727-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55727-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55727-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().