A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection
Abstract Adoptive natural killer cell therapy (ANKCT) harbors great potential for combating postsurgical hepatocellular carcinoma (HCC) recurrence, but its efficacy is limited by tumor microenvironment (TME)-meditated repression on NK cell function and insufficient NK cell homing to tumor sites. The...
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BMC
2025-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03424-9 |
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| author | Yusheng Cheng Yihang Gong Xin Li Fanxin Zeng Bo Liu Wenjie Chen Feng Zhang Haofei Chen Weixiong Zhu Hui Li Lei Zhou Tiangen Wu Wence Zhou |
| author_facet | Yusheng Cheng Yihang Gong Xin Li Fanxin Zeng Bo Liu Wenjie Chen Feng Zhang Haofei Chen Weixiong Zhu Hui Li Lei Zhou Tiangen Wu Wence Zhou |
| author_sort | Yusheng Cheng |
| collection | DOAJ |
| description | Abstract Adoptive natural killer cell therapy (ANKCT) harbors great potential for combating postsurgical hepatocellular carcinoma (HCC) recurrence, but its efficacy is limited by tumor microenvironment (TME)-meditated repression on NK cell function and insufficient NK cell homing to tumor sites. Therefore, herein we develop a nanocomposite sprayable self-gelling powder enabling liver-localized codelivery of three FDA-approved drugs including calcitriol (Cal), gemcitabine (Gem), and tazemetostat (Taz) to address these challenges. This powder can be laparoscopically spread to liver wound sites, where it rapidly absorbs interfacial liquid to form a bulk adhesive pressure-resistant hydrogel in situ, implying its application potential in minimally surgery. Moreover, its application to liver resection bed significantly sensitizes allogenic NK and EpCAM chimeric antigen receptor modified-NK-92 (EpCAM-CAR-NK) cell infusion to prevent HCC recurrence in orthotopic Heap1-6 tumor-bearing and patient-derived tumor xenograft (PDX) HCC murine models. Additionally, this powder can allow for an effective hemostatic effect in rat and porcine models due to its powerful tissue adhesion-seal and erythrocyte-aggregating effects. Altogether, our newly developed hemostatic self-gelling powder can significantly sensitize ANKCT to combat HCC recurrence in a manner compatible with surgical treatment of HCC. Graphical abstract |
| format | Article |
| id | doaj-art-5b612c22007a4e22894b1dcb590f77c2 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-5b612c22007a4e22894b1dcb590f77c22025-08-20T03:53:46ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112210.1186/s12951-025-03424-9A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresectionYusheng Cheng0Yihang Gong1Xin Li2Fanxin Zeng3Bo Liu4Wenjie Chen5Feng Zhang6Haofei Chen7Weixiong Zhu8Hui Li9Lei Zhou10Tiangen Wu11Wence Zhou12The Second Clinical Medical School of Lanzhou UniversityDepartment of Hepatic Surgery and Liver Transplantation Center, Organ Transplantation Institute, Organ Transplantation Research Center of Guangdong Province, Guangdong Province Engineering Laboratory for Transplantation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen UniversityThe Second Clinical Medical School of Lanzhou UniversityDepartment of Hepatic Surgery and Liver Transplantation Center, Organ Transplantation Institute, Organ Transplantation Research Center of Guangdong Province, Guangdong Province Engineering Laboratory for Transplantation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen UniversityThe Second Clinical Medical School of Lanzhou UniversityBiotherapy Centre & Cell-gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-sen UniversityBiotherapy Centre & Cell-gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-sen UniversityGansu Province Precision Diagnosis and Treatment Engineering Research Center of Hepatobiliary Pancreatic Diseases, Gansu Province Key Laboratory of Environmental OncologyThe Second Clinical Medical School of Lanzhou UniversityDepartment of Hepatobiliary Pancreatic Tumor Center, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalGuangzhou Key Laboratory of Spine Disease Prevention and Treatment, Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityThe Second Clinical Medical School of Lanzhou UniversityAbstract Adoptive natural killer cell therapy (ANKCT) harbors great potential for combating postsurgical hepatocellular carcinoma (HCC) recurrence, but its efficacy is limited by tumor microenvironment (TME)-meditated repression on NK cell function and insufficient NK cell homing to tumor sites. Therefore, herein we develop a nanocomposite sprayable self-gelling powder enabling liver-localized codelivery of three FDA-approved drugs including calcitriol (Cal), gemcitabine (Gem), and tazemetostat (Taz) to address these challenges. This powder can be laparoscopically spread to liver wound sites, where it rapidly absorbs interfacial liquid to form a bulk adhesive pressure-resistant hydrogel in situ, implying its application potential in minimally surgery. Moreover, its application to liver resection bed significantly sensitizes allogenic NK and EpCAM chimeric antigen receptor modified-NK-92 (EpCAM-CAR-NK) cell infusion to prevent HCC recurrence in orthotopic Heap1-6 tumor-bearing and patient-derived tumor xenograft (PDX) HCC murine models. Additionally, this powder can allow for an effective hemostatic effect in rat and porcine models due to its powerful tissue adhesion-seal and erythrocyte-aggregating effects. Altogether, our newly developed hemostatic self-gelling powder can significantly sensitize ANKCT to combat HCC recurrence in a manner compatible with surgical treatment of HCC. Graphical abstracthttps://doi.org/10.1186/s12951-025-03424-9Nanocomposite hydrogelDrug deliveryHemostasisHepatocellular carcinomaNK cell therapy |
| spellingShingle | Yusheng Cheng Yihang Gong Xin Li Fanxin Zeng Bo Liu Wenjie Chen Feng Zhang Haofei Chen Weixiong Zhu Hui Li Lei Zhou Tiangen Wu Wence Zhou A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection Journal of Nanobiotechnology Nanocomposite hydrogel Drug delivery Hemostasis Hepatocellular carcinoma NK cell therapy |
| title | A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| title_full | A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| title_fullStr | A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| title_full_unstemmed | A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| title_short | A spreadable self-gelling hemostatic powder sensitizes CAR-NK cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| title_sort | spreadable self gelling hemostatic powder sensitizes car nk cell therapy to prevent hepatocellular carcinoma recurrence postresection |
| topic | Nanocomposite hydrogel Drug delivery Hemostasis Hepatocellular carcinoma NK cell therapy |
| url | https://doi.org/10.1186/s12951-025-03424-9 |
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