An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma
Abstract Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin‐Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage...
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10430 |
| _version_ | 1797777263171731456 |
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| author | Rui Cai Meng Wang Meiyuan Liu Xiongjie Zhu Longbao Feng Zhongjian Yu Xia Yang Zhiwu Zhang Huili Guo Rui Guo Yanfang Zheng |
| author_facet | Rui Cai Meng Wang Meiyuan Liu Xiongjie Zhu Longbao Feng Zhongjian Yu Xia Yang Zhiwu Zhang Huili Guo Rui Guo Yanfang Zheng |
| author_sort | Rui Cai |
| collection | DOAJ |
| description | Abstract Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin‐Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage infiltration in LUAD. Thus, we have developed an internalizing‐RGD (iRGD)‐conjugated gold nanoparticle (AuNP) system which carries siCDK7 to activate the antitumor immune response. The iRGD‐conjugated AuNP/siCDK7 system exhibited good tumor targeting performance and photothermal effects. The AuNP/siCDK7 system with excellent biosafety exerted a significant photothermal antitumor effect by inducing tumor cell necroptosis. Furthermore, the AuNP/siCDK7 system ameliorated the immunosuppressive microenvironment and enhanced the efficacy of anti‐PD‐1 treatment by increasing CD8+ T cell infiltration and decreasing M2 macrophage infiltration. Hence, this iRGD‐conjugated AuNP/siCDK7 system is a potential treatment strategy for lung adenocarcinoma, which exerts its effects by triggering tumor cell necroptosis and immunotherapeutic responses. |
| first_indexed | 2024-03-12T23:01:38Z |
| format | Article |
| id | doaj.art-4bae68ce7de94fee81838412c5fd43f9 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-12T23:01:38Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-4bae68ce7de94fee81838412c5fd43f92023-07-19T09:59:03ZengWileyBioengineering & Translational Medicine2380-67612023-07-0184n/an/a10.1002/btm2.10430An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinomaRui Cai0Meng Wang1Meiyuan Liu2Xiongjie Zhu3Longbao Feng4Zhongjian Yu5Xia Yang6Zhiwu Zhang7Huili Guo8Rui Guo9Yanfang Zheng10Department of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering Jinan University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering Jinan University Guangzhou ChinaDepartment of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou ChinaAbstract Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin‐Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage infiltration in LUAD. Thus, we have developed an internalizing‐RGD (iRGD)‐conjugated gold nanoparticle (AuNP) system which carries siCDK7 to activate the antitumor immune response. The iRGD‐conjugated AuNP/siCDK7 system exhibited good tumor targeting performance and photothermal effects. The AuNP/siCDK7 system with excellent biosafety exerted a significant photothermal antitumor effect by inducing tumor cell necroptosis. Furthermore, the AuNP/siCDK7 system ameliorated the immunosuppressive microenvironment and enhanced the efficacy of anti‐PD‐1 treatment by increasing CD8+ T cell infiltration and decreasing M2 macrophage infiltration. Hence, this iRGD‐conjugated AuNP/siCDK7 system is a potential treatment strategy for lung adenocarcinoma, which exerts its effects by triggering tumor cell necroptosis and immunotherapeutic responses.https://doi.org/10.1002/btm2.10430CDK7gold nanoparticleslung adenocarcinomaM2 macrophagesnecroptosis |
| spellingShingle | Rui Cai Meng Wang Meiyuan Liu Xiongjie Zhu Longbao Feng Zhongjian Yu Xia Yang Zhiwu Zhang Huili Guo Rui Guo Yanfang Zheng An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma Bioengineering & Translational Medicine CDK7 gold nanoparticles lung adenocarcinoma M2 macrophages necroptosis |
| title | An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| title_full | An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| title_fullStr | An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| title_full_unstemmed | An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| title_short | An iRGD‐conjugated photothermal therapy‐responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| title_sort | irgd conjugated photothermal therapy responsive gold nanoparticle system carrying sicdk7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma |
| topic | CDK7 gold nanoparticles lung adenocarcinoma M2 macrophages necroptosis |
| url | https://doi.org/10.1002/btm2.10430 |
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