Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response
Abstract The immunosuppressive residual tumor microenvironment (IRTM) is a key factor in the high recurrence and metastasis rates of hepatocellular carcinoma (HCC) after microwave ablation (MWA). Cholesterol‐rich tumor fragments significantly contribute to IRTM deterioration. This study developed a...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202406975 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540912578723840 |
|---|---|
| author | Lin Shen Zhijuan Yang Yi Zhong Yanran Bi Junchao Yu Qinwei Lu Yanping Su Xiaoxiao Chen Zhongwei Zhao Gaofeng Shu Minjiang Chen Liang Cheng Liangzhu Feng Chenying Lu Zhuang Liu Jiansong Ji |
| author_facet | Lin Shen Zhijuan Yang Yi Zhong Yanran Bi Junchao Yu Qinwei Lu Yanping Su Xiaoxiao Chen Zhongwei Zhao Gaofeng Shu Minjiang Chen Liang Cheng Liangzhu Feng Chenying Lu Zhuang Liu Jiansong Ji |
| author_sort | Lin Shen |
| collection | DOAJ |
| description | Abstract The immunosuppressive residual tumor microenvironment (IRTM) is a key factor in the high recurrence and metastasis rates of hepatocellular carcinoma (HCC) after microwave ablation (MWA). Cholesterol‐rich tumor fragments significantly contribute to IRTM deterioration. This study developed a cholesterol‐targeted catalytic hydrogel, DA‐COD‐OD‐HCS, to enhance the synergy between MWA and immune checkpoint inhibitors (ICIs) for HCC treatment. Cholesterol oxidase (COD), modified with dimethyl maleic anhydride (DA) for release in acidic IRTM, is used to degrade cholesterol. Oxydextran (OD) and hemin‐chitosan (HCS) formed a dual network gel, ensuring long‐term fixation of COD and hemin in the IRTM post‐MWA. In both in vitro and in vivo HCC models, DA‐COD‐OD‐HCS effectively released COD, degraded cholesterol, and induced tumor cell ferroptosis, enhancing the antitumor immune response. Combined with anti‐PD‐L1 immunotherapy, this strategy inhibited primary tumor growth and distant metastases, without side effects on adjacent tissues. This work highlights that cholesterol‐targeting catalytic hydrogels fueled by tumor debris can significantly improve the efficacy of MWA and ICIs, offering a novel therapeutic approach for HCC. |
| format | Article |
| id | doaj-art-b4d0185723124e75b6997bd55f9ce570 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b4d0185723124e75b6997bd55f9ce5702025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202406975Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune ResponseLin Shen0Zhijuan Yang1Yi Zhong2Yanran Bi3Junchao Yu4Qinwei Lu5Yanping Su6Xiaoxiao Chen7Zhongwei Zhao8Gaofeng Shu9Minjiang Chen10Liang Cheng11Liangzhu Feng12Chenying Lu13Zhuang Liu14Jiansong Ji15Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaInstitute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou Jiangsu 215123 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaInstitute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou Jiangsu 215123 P. R. ChinaInstitute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou Jiangsu 215123 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaInstitute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou Jiangsu 215123 P. R. ChinaZhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University Lishui 323000 P. R. ChinaAbstract The immunosuppressive residual tumor microenvironment (IRTM) is a key factor in the high recurrence and metastasis rates of hepatocellular carcinoma (HCC) after microwave ablation (MWA). Cholesterol‐rich tumor fragments significantly contribute to IRTM deterioration. This study developed a cholesterol‐targeted catalytic hydrogel, DA‐COD‐OD‐HCS, to enhance the synergy between MWA and immune checkpoint inhibitors (ICIs) for HCC treatment. Cholesterol oxidase (COD), modified with dimethyl maleic anhydride (DA) for release in acidic IRTM, is used to degrade cholesterol. Oxydextran (OD) and hemin‐chitosan (HCS) formed a dual network gel, ensuring long‐term fixation of COD and hemin in the IRTM post‐MWA. In both in vitro and in vivo HCC models, DA‐COD‐OD‐HCS effectively released COD, degraded cholesterol, and induced tumor cell ferroptosis, enhancing the antitumor immune response. Combined with anti‐PD‐L1 immunotherapy, this strategy inhibited primary tumor growth and distant metastases, without side effects on adjacent tissues. This work highlights that cholesterol‐targeting catalytic hydrogels fueled by tumor debris can significantly improve the efficacy of MWA and ICIs, offering a novel therapeutic approach for HCC.https://doi.org/10.1002/advs.202406975cholesterol‐targeted catalytic hydrogelferroptosisICIsMWAsynergistic therapy |
| spellingShingle | Lin Shen Zhijuan Yang Yi Zhong Yanran Bi Junchao Yu Qinwei Lu Yanping Su Xiaoxiao Chen Zhongwei Zhao Gaofeng Shu Minjiang Chen Liang Cheng Liangzhu Feng Chenying Lu Zhuang Liu Jiansong Ji Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response Advanced Science cholesterol‐targeted catalytic hydrogel ferroptosis ICIs MWA synergistic therapy |
| title | Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response |
| title_full | Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response |
| title_fullStr | Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response |
| title_full_unstemmed | Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response |
| title_short | Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response |
| title_sort | cholesterol targeted catalytic hydrogel fueled by tumor debris can enhance microwave ablation therapy and anti tumor immune response |
| topic | cholesterol‐targeted catalytic hydrogel ferroptosis ICIs MWA synergistic therapy |
| url | https://doi.org/10.1002/advs.202406975 |
| work_keys_str_mv | AT linshen cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT zhijuanyang cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT yizhong cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT yanranbi cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT junchaoyu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT qinweilu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT yanpingsu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT xiaoxiaochen cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT zhongweizhao cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT gaofengshu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT minjiangchen cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT liangcheng cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT liangzhufeng cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT chenyinglu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT zhuangliu cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse AT jiansongji cholesteroltargetedcatalytichydrogelfueledbytumordebriscanenhancemicrowaveablationtherapyandantitumorimmuneresponse |