MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression
Abstract Background Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Methods Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), t...
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BMC
2025-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04456-6 |
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| author | Yanxia Chen Meijuan He Lei Cui Jianguo Zhang Hanpeng Huang Zhimin Tao |
| author_facet | Yanxia Chen Meijuan He Lei Cui Jianguo Zhang Hanpeng Huang Zhimin Tao |
| author_sort | Yanxia Chen |
| collection | DOAJ |
| description | Abstract Background Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Methods Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model. Results Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors. Conclusions Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options. Clinical trial number Not applicable. |
| format | Article |
| id | doaj-art-c735301f29b54d4a8b8f63ee69fcde24 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-c735301f29b54d4a8b8f63ee69fcde242025-08-20T03:45:24ZengBMCStem Cell Research & Therapy1757-65122025-07-0116111510.1186/s13287-025-04456-6MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expressionYanxia Chen0Meijuan He1Lei Cui2Jianguo Zhang3Hanpeng Huang4Zhimin Tao5Department of Emergency Medicine, Affiliated Hospital of Jiangsu UniversityDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Jiangsu UniversityDepartment of General Surgery, Affiliated Hospital of Jiangsu UniversityDepartment of Emergency Medicine, Affiliated Hospital of Jiangsu UniversityDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Jiangsu UniversityDepartment of Emergency Medicine, Affiliated Hospital of Jiangsu UniversityAbstract Background Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Methods Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model. Results Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors. Conclusions Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options. Clinical trial number Not applicable.https://doi.org/10.1186/s13287-025-04456-6Small extracellular vesiclesMicroRNAColorectal cancerFascin actin-bundling protein 1Near-infrared II fluorescence |
| spellingShingle | Yanxia Chen Meijuan He Lei Cui Jianguo Zhang Hanpeng Huang Zhimin Tao MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression Stem Cell Research & Therapy Small extracellular vesicles MicroRNA Colorectal cancer Fascin actin-bundling protein 1 Near-infrared II fluorescence |
| title | MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression |
| title_full | MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression |
| title_fullStr | MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression |
| title_full_unstemmed | MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression |
| title_short | MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression |
| title_sort | mir 145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin bundling protein 1 expression |
| topic | Small extracellular vesicles MicroRNA Colorectal cancer Fascin actin-bundling protein 1 Near-infrared II fluorescence |
| url | https://doi.org/10.1186/s13287-025-04456-6 |
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