Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis
Abstract Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03091-w |
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| author | Xinyan Hao Yucheng Tang Wenjie Xu Ming Wang Jiayi Liu Yongjiang Li Jun He Yanjin Peng Pengcheng Sun Dehua Liao Xiongbin Hu Tiantian Tang Min Zhou Ruyue Han Jiemin Wang João Conde Daxiong Xiang Junyong Wu |
| author_facet | Xinyan Hao Yucheng Tang Wenjie Xu Ming Wang Jiayi Liu Yongjiang Li Jun He Yanjin Peng Pengcheng Sun Dehua Liao Xiongbin Hu Tiantian Tang Min Zhou Ruyue Han Jiemin Wang João Conde Daxiong Xiang Junyong Wu |
| author_sort | Xinyan Hao |
| collection | DOAJ |
| description | Abstract Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM. |
| format | Article |
| id | doaj-art-bf484c3b7e314975a52b75f91d42bf8d |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-bf484c3b7e314975a52b75f91d42bf8d2025-01-19T12:37:46ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111610.1186/s12951-025-03091-wEngineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosisXinyan Hao0Yucheng Tang1Wenjie Xu2Ming Wang3Jiayi Liu4Yongjiang Li5Jun He6Yanjin Peng7Pengcheng Sun8Dehua Liao9Xiongbin Hu10Tiantian Tang11Min Zhou12Ruyue Han13Jiemin Wang14João Conde15Daxiong Xiang16Junyong Wu17Department of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Neurosurgery The Second Xiangya Hospital, Central South UniversityDepartment of Oncology, The Second Xiangya Hospital, Central South UniversityCenter for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of General Surgery The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, School of Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityRegenerative Medicine Institute, School of Medicine, University of GalwayToxOmics, NOVA Medical School, Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de LisboaDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy The Second Xiangya Hospital, Central South UniversityAbstract Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM.https://doi.org/10.1186/s12951-025-03091-wGlioblastomaPyroptosisCisplatinProgrammed death-1Chemo-immunotherapy |
| spellingShingle | Xinyan Hao Yucheng Tang Wenjie Xu Ming Wang Jiayi Liu Yongjiang Li Jun He Yanjin Peng Pengcheng Sun Dehua Liao Xiongbin Hu Tiantian Tang Min Zhou Ruyue Han Jiemin Wang João Conde Daxiong Xiang Junyong Wu Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis Journal of Nanobiotechnology Glioblastoma Pyroptosis Cisplatin Programmed death-1 Chemo-immunotherapy |
| title | Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis |
| title_full | Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis |
| title_fullStr | Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis |
| title_full_unstemmed | Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis |
| title_short | Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis |
| title_sort | engineered biomimetic cisplatin polyphenol nanocomplex for chemo immunotherapy of glioblastoma by inducing pyroptosis |
| topic | Glioblastoma Pyroptosis Cisplatin Programmed death-1 Chemo-immunotherapy |
| url | https://doi.org/10.1186/s12951-025-03091-w |
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