Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer
Abstract Background The efficacy of current therapies for ovarian cancer is limited due to the multilevel and complex tumor microenvironment (TME), which induces drug resistance and tumor progression in a single treatment regimen. Additionally, poor targeting and insufficient tissue penetration are...
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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/s12951-025-03165-9 |
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| author | Yuwei Yao Jiarui Zhang Kexin Huang Yingying Peng Shuangshuang Cheng Shuangge Liu Ting Zhou Jinhua Chen Haojia Li Yingchao Zhao Hongbo Wang |
| author_facet | Yuwei Yao Jiarui Zhang Kexin Huang Yingying Peng Shuangshuang Cheng Shuangge Liu Ting Zhou Jinhua Chen Haojia Li Yingchao Zhao Hongbo Wang |
| author_sort | Yuwei Yao |
| collection | DOAJ |
| description | Abstract Background The efficacy of current therapies for ovarian cancer is limited due to the multilevel and complex tumor microenvironment (TME), which induces drug resistance and tumor progression in a single treatment regimen. Additionally, poor targeting and insufficient tissue penetration are important constraints in ovarian cancer treatment. Result We constructed PH20-overexpressing cancer-associated fibroblast (CAF)-cancer hybrid-cell membrane vesicles (PH20/CCM) for the dual-targeted delivery of carboplatin (CBP) and siRNA targeting p65 (sip65) loaded on the poly (dimethyl diallyl ammonium chloride) (PDDA)-modified MXene (PMXene), named PMXene@CBP-sip65 (PMCS). The nanoparticle PH20/CCM@PMCS could penetrate the extracellular matrix of tumor tissues and target both cancer cells and CAFs. After tumor cell internalization, these nanoparticles significantly inhibited cancer cell proliferation, generated reactive oxygen species, induced endoplasmic reticulum stress, and triggered immunogenic cell death. After CAF internalization, they inhibited pro-tumor factor release and activated immune effects, promoting immune system infiltration. In an experiment with ID8 homograft-carrying mice, PH20/CCM@PMCS significantly improved tumor inhibition and enhanced immune infiltration in tumor tissues. Conclusion These new therapeutic nanoparticles can simultaneously target tumor cells, CAFs, immune cells, and the extracellular matrix, thereby increasing treatment sensitivity and improving the TME. Therefore, these TME-regulating nanoparticles, combining specificity, efficiency, and effectiveness, provide new insights into ovarian cancer treatment. Graphical Abstract |
| format | Article |
| id | doaj-art-01fb099f7b16419b80410d78b27d9044 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-01fb099f7b16419b80410d78b27d90442025-02-09T12:53:04ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112010.1186/s12951-025-03165-9Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancerYuwei Yao0Jiarui Zhang1Kexin Huang2Yingying Peng3Shuangshuang Cheng4Shuangge Liu5Ting Zhou6Jinhua Chen7Haojia Li8Yingchao Zhao9Hongbo Wang10Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background The efficacy of current therapies for ovarian cancer is limited due to the multilevel and complex tumor microenvironment (TME), which induces drug resistance and tumor progression in a single treatment regimen. Additionally, poor targeting and insufficient tissue penetration are important constraints in ovarian cancer treatment. Result We constructed PH20-overexpressing cancer-associated fibroblast (CAF)-cancer hybrid-cell membrane vesicles (PH20/CCM) for the dual-targeted delivery of carboplatin (CBP) and siRNA targeting p65 (sip65) loaded on the poly (dimethyl diallyl ammonium chloride) (PDDA)-modified MXene (PMXene), named PMXene@CBP-sip65 (PMCS). The nanoparticle PH20/CCM@PMCS could penetrate the extracellular matrix of tumor tissues and target both cancer cells and CAFs. After tumor cell internalization, these nanoparticles significantly inhibited cancer cell proliferation, generated reactive oxygen species, induced endoplasmic reticulum stress, and triggered immunogenic cell death. After CAF internalization, they inhibited pro-tumor factor release and activated immune effects, promoting immune system infiltration. In an experiment with ID8 homograft-carrying mice, PH20/CCM@PMCS significantly improved tumor inhibition and enhanced immune infiltration in tumor tissues. Conclusion These new therapeutic nanoparticles can simultaneously target tumor cells, CAFs, immune cells, and the extracellular matrix, thereby increasing treatment sensitivity and improving the TME. Therefore, these TME-regulating nanoparticles, combining specificity, efficiency, and effectiveness, provide new insights into ovarian cancer treatment. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03165-9Cancer-associated fibroblastsTumor microenvironmentMembrane-coated nanoparticlesTargeted therapy |
| spellingShingle | Yuwei Yao Jiarui Zhang Kexin Huang Yingying Peng Shuangshuang Cheng Shuangge Liu Ting Zhou Jinhua Chen Haojia Li Yingchao Zhao Hongbo Wang Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer Journal of Nanobiotechnology Cancer-associated fibroblasts Tumor microenvironment Membrane-coated nanoparticles Targeted therapy |
| title | Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer |
| title_full | Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer |
| title_fullStr | Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer |
| title_full_unstemmed | Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer |
| title_short | Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer |
| title_sort | engineered caf cancer cell hybrid membrane biomimetic dual targeted integrated platform for multi dimensional treatment of ovarian cancer |
| topic | Cancer-associated fibroblasts Tumor microenvironment Membrane-coated nanoparticles Targeted therapy |
| url | https://doi.org/10.1186/s12951-025-03165-9 |
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