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 |
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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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| _version_ | 1841559331597713408 |
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| author | Xueyi Hu Yichun Wang Ruohan Wang Yiyao Pu Rongrong Jin Yu Nie Xintao Shuai |
| author_facet | Xueyi Hu Yichun Wang Ruohan Wang Yiyao Pu Rongrong Jin Yu Nie Xintao Shuai |
| author_sort | Xueyi Hu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fe3f722ba8bd40b8b2eb5f3e47366bef |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fe3f722ba8bd40b8b2eb5f3e47366bef2025-01-05T12:37:07ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55727-4The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapyXueyi Hu0Yichun Wang1Ruohan Wang2Yiyao Pu3Rongrong Jin4Yu Nie5Xintao Shuai6National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan UniversityNanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55727-4 |
| spellingShingle | Xueyi Hu Yichun Wang Ruohan Wang Yiyao Pu Rongrong Jin Yu Nie Xintao Shuai The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy Nature Communications |
| title | The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy |
| title_full | The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy |
| title_fullStr | The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy |
| title_full_unstemmed | The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy |
| title_short | The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy |
| title_sort | hybrid lipoplex induces cytoskeletal rearrangement via autophagy rhoa signaling pathway for enhanced anticancer gene therapy |
| url | https://doi.org/10.1038/s41467-024-55727-4 |
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