The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer 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 d...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55727-4 |
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| Summary: | 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. |
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| ISSN: | 2041-1723 |