Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy
Abstract Background Vascular abnormalities and hypoxia in solid tumors limit the efficacy of chimeric antigen receptor (CAR) T-cell therapy. This study proposes a biomimic nanoenzyme, Lenv@BSA-PtNPs, combining platinum nanoparticles (PtNPs) and lenvatinib, to address these challenges in a hepatocell...
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BMC
2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06636-7 |
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| author | Yu Xu Jianping Liao Jiahong Wang Yuan Gao Yuan Wu Meiqin Gao Wenwen Liu Da Zhang Wenmin Zhang Aimin Huang |
| author_facet | Yu Xu Jianping Liao Jiahong Wang Yuan Gao Yuan Wu Meiqin Gao Wenwen Liu Da Zhang Wenmin Zhang Aimin Huang |
| author_sort | Yu Xu |
| collection | DOAJ |
| description | Abstract Background Vascular abnormalities and hypoxia in solid tumors limit the efficacy of chimeric antigen receptor (CAR) T-cell therapy. This study proposes a biomimic nanoenzyme, Lenv@BSA-PtNPs, combining platinum nanoparticles (PtNPs) and lenvatinib, to address these challenges in a hepatocellular carcinoma (HCC) nonobese diabetic (NOD) mice model. Methods Lenv@BSA-PtNPs were designed using albumin as a solubilizer, embedding lenvatinib via hydrophobic interactions and facilitating in situ PtNPs generation. The nanoenzyme functions as a catalase, converting H2O2 to O2, downregulating hypoxia-inducible factor (HIF-1), and normalizing tumor vasculature. Its efficacy was evaluated in a glypican-3 (GPC3)-CAR T-cell therapy model for HCC. Results Lenv@BSA-PtNPs significantly improved tumor oxygenation, normalized vasculature, and enhanced GPC3-CAR T-cell infiltration into tumors. This led to potent antitumor effects and prolonged survival in the HCC mouse model. Conclusions Lenv@BSA-PtNPs provide a simple and effective strategy to enhance CAR-T cell accumulation and efficacy by ameliorating hypoxia and normalizing tumor vasculature, offering a promising approach for improving CAR-T therapy in solid tumors. |
| format | Article |
| id | doaj-art-a56a594fcb0044ea919f1febebdcea7a |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-a56a594fcb0044ea919f1febebdcea7a2025-08-20T02:07:41ZengBMCJournal of Translational Medicine1479-58762025-06-0123111510.1186/s12967-025-06636-7Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapyYu Xu0Jianping Liao1Jiahong Wang2Yuan Gao3Yuan Wu4Meiqin Gao5Wenwen Liu6Da Zhang7Wenmin Zhang8Aimin Huang9Department of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical UniversityAbstract Background Vascular abnormalities and hypoxia in solid tumors limit the efficacy of chimeric antigen receptor (CAR) T-cell therapy. This study proposes a biomimic nanoenzyme, Lenv@BSA-PtNPs, combining platinum nanoparticles (PtNPs) and lenvatinib, to address these challenges in a hepatocellular carcinoma (HCC) nonobese diabetic (NOD) mice model. Methods Lenv@BSA-PtNPs were designed using albumin as a solubilizer, embedding lenvatinib via hydrophobic interactions and facilitating in situ PtNPs generation. The nanoenzyme functions as a catalase, converting H2O2 to O2, downregulating hypoxia-inducible factor (HIF-1), and normalizing tumor vasculature. Its efficacy was evaluated in a glypican-3 (GPC3)-CAR T-cell therapy model for HCC. Results Lenv@BSA-PtNPs significantly improved tumor oxygenation, normalized vasculature, and enhanced GPC3-CAR T-cell infiltration into tumors. This led to potent antitumor effects and prolonged survival in the HCC mouse model. Conclusions Lenv@BSA-PtNPs provide a simple and effective strategy to enhance CAR-T cell accumulation and efficacy by ameliorating hypoxia and normalizing tumor vasculature, offering a promising approach for improving CAR-T therapy in solid tumors.https://doi.org/10.1186/s12967-025-06636-7NanoenzymeVascular normalizationHypoxiaGPC3-CAR T cells immunity |
| spellingShingle | Yu Xu Jianping Liao Jiahong Wang Yuan Gao Yuan Wu Meiqin Gao Wenwen Liu Da Zhang Wenmin Zhang Aimin Huang Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy Journal of Translational Medicine Nanoenzyme Vascular normalization Hypoxia GPC3-CAR T cells immunity |
| title | Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy |
| title_full | Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy |
| title_fullStr | Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy |
| title_full_unstemmed | Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy |
| title_short | Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy |
| title_sort | bidirectional roles of nanoenzymes in enhancing gpc3 car t cell infiltration and cancer immunotherapy |
| topic | Nanoenzyme Vascular normalization Hypoxia GPC3-CAR T cells immunity |
| url | https://doi.org/10.1186/s12967-025-06636-7 |
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