Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota
Abstract Despite the approval of several artificial nanotherapeutics for the treatment of triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and the high cost of large-scale production, still restrict their long-term appl...
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03139-x |
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| author | Min Yang Jia Guo Jinxian Li Shuyue Wang Yuan Sun Ying Liu Yinghua Peng |
| author_facet | Min Yang Jia Guo Jinxian Li Shuyue Wang Yuan Sun Ying Liu Yinghua Peng |
| author_sort | Min Yang |
| collection | DOAJ |
| description | Abstract Despite the approval of several artificial nanotherapeutics for the treatment of triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and the high cost of large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in cancer therapy due to their negligible systemic toxicity, high bioavailability and cost- effectiveness. In this study, we developed an alternative strategy to inhibit TNBC via Platycodon grandiflorum (PG)-derived extracellular vesicles (PGEVs). The PGEVs were isolated by ultracentrifugation and sucrose gradient centrifugation method and contained adequate functional components such as proteins, lipids, RNAs and active molecules. PGEVs exhibited remarkable stability, tolerating acidic digestion and undergoing minimal changes in simulated gastrointestinal fluid. They were efficiently taken up by tumor cells and induced increased production of reactive oxygen species (ROS), leading to tumor cell proliferation inhibition and apoptosis, particularly in the TNBC cell line 4T1. Additionally, PGEVs facilitated the polarization of tumor-associated macrophages (TAMs) toward M1 phenotype and increased the secretion of pro-inflammatory cytokines. Further in vivo investigations revealed that PGEVs efficiently accumulated in 4T1 tumors and exerted significant therapeutic effects through boosting systemic anti-tumor immune responses and modulating the gut microbiota whether administered orally or intravenously (i.v.). In conclusion, these findings highlight PGEVs as a promising natural, biocompatible and efficient nanotherapeutic candidate for treating TNBC. Graphical Abstract |
| format | Article |
| id | doaj-art-8dc918a0e0a64011b7953551fe0fa9a7 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-8dc918a0e0a64011b7953551fe0fa9a72025-02-09T12:53:05ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112510.1186/s12951-025-03139-xPlatycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiotaMin Yang0Jia Guo1Jinxian Li2Shuyue Wang3Yuan Sun4Ying Liu5Yinghua Peng6Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesInstitute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesInstitute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesSchool of Chemistry and Life Science, Changchun University of TechnologyInstitute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesInstitute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesInstitute of Special Animal and Plant Sciences, Chinese Academy of Agricultural SciencesAbstract Despite the approval of several artificial nanotherapeutics for the treatment of triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and the high cost of large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in cancer therapy due to their negligible systemic toxicity, high bioavailability and cost- effectiveness. In this study, we developed an alternative strategy to inhibit TNBC via Platycodon grandiflorum (PG)-derived extracellular vesicles (PGEVs). The PGEVs were isolated by ultracentrifugation and sucrose gradient centrifugation method and contained adequate functional components such as proteins, lipids, RNAs and active molecules. PGEVs exhibited remarkable stability, tolerating acidic digestion and undergoing minimal changes in simulated gastrointestinal fluid. They were efficiently taken up by tumor cells and induced increased production of reactive oxygen species (ROS), leading to tumor cell proliferation inhibition and apoptosis, particularly in the TNBC cell line 4T1. Additionally, PGEVs facilitated the polarization of tumor-associated macrophages (TAMs) toward M1 phenotype and increased the secretion of pro-inflammatory cytokines. Further in vivo investigations revealed that PGEVs efficiently accumulated in 4T1 tumors and exerted significant therapeutic effects through boosting systemic anti-tumor immune responses and modulating the gut microbiota whether administered orally or intravenously (i.v.). In conclusion, these findings highlight PGEVs as a promising natural, biocompatible and efficient nanotherapeutic candidate for treating TNBC. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03139-xPlatycodon grandiflorumPlant-derived extracellular vesiclesTNBCTumor immunotherapyGut microbiota modulation |
| spellingShingle | Min Yang Jia Guo Jinxian Li Shuyue Wang Yuan Sun Ying Liu Yinghua Peng Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota Journal of Nanobiotechnology Platycodon grandiflorum Plant-derived extracellular vesicles TNBC Tumor immunotherapy Gut microbiota modulation |
| title | Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| title_full | Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| title_fullStr | Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| title_full_unstemmed | Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| title_short | Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| title_sort | platycodon grandiflorum derived extracellular vesicles suppress triple negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota |
| topic | Platycodon grandiflorum Plant-derived extracellular vesicles TNBC Tumor immunotherapy Gut microbiota modulation |
| url | https://doi.org/10.1186/s12951-025-03139-x |
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