1. The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy.
- Author
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Hu, Xueyi, Wang, Yichun, Wang, Ruohan, Pu, Yiyao, Jin, Rongrong, Nie, Yu, and Shuai, Xintao
- Subjects
CATIONIC lipids ,GOLD nanoparticles ,HEPATOCELLULAR carcinoma ,GOLD coatings ,GENE therapy - 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. Delivering plasmid DNA to solid tumors is challenging since it demands more transport steps than other genetic materials. Here this group designs a hybrid lipoplex for co-delivering p53 plasmid along with MDM2 inhibitor sp141 to hepatocellular carcinoma and lung carcinoma for synergistic anti-tumor treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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