A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy
Abstract To overcome the problems of Gd‐based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo‐charging system‐like GBCA is designed and construc...
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| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202410432 |
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| author | Bin Ren Sihua Yan Zongheng Li Ya Huang Haobin Cai Jing Yang Qingdeng Fan Chunmei Chen Fanchao Que Guochao Wu Lin Huang Ruilong Zhou Jiaoyang Zhu Chenggong Yan Gang Liu Zheyu Shen Shipeng Ning |
| author_facet | Bin Ren Sihua Yan Zongheng Li Ya Huang Haobin Cai Jing Yang Qingdeng Fan Chunmei Chen Fanchao Que Guochao Wu Lin Huang Ruilong Zhou Jiaoyang Zhu Chenggong Yan Gang Liu Zheyu Shen Shipeng Ning |
| author_sort | Bin Ren |
| collection | DOAJ |
| description | Abstract To overcome the problems of Gd‐based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo‐charging system‐like GBCA is designed and constructed for magnetic resonance imaging (MRI) guided STING pathway‐activated cancer immunotherapy. Poly(acrylic acid) (PAA) is used to coordinate with Gd3+, forming a Gd/PAA macrochelate. Both Gd/PAA macrochelate and SR717 are conjugated to cystamine (CA) to obtain SR717‐CA@Gd/PAA self‐assembled nanoparticles (SAN), which are termed as Turbo S because of its similarity with the Turbo‐charging system of cars. After accumulation in tumors and internalization in tumor cells, the disulfide linkage in Turbo S undergoes a cleavage process catalyzed by glutathione (GSH), leading to the release of Gd/PAA and SR717. The released Gd/PAA gain a high r1 value (17.11 mM−1 s−1 at 7.0 T; 57.81 mM−1 s−1 at 3.0 T), indicating its strong T1 imaging capability. Turbo S with a low dosage of SR717 (8.9 mg kg−1) achieved a higher tumor immunotherapeutic efficacy than free SR717 with a high dosage (30 mg kg−1). The excellent delivery efficiency, high tumor treatment efficacy, and superior biosafety demonstrate that the Turbo S can be used as a promising candidate for tumor immunotherapy. |
| format | Article |
| id | doaj-art-ab0ed5e872804293ad7dab7125234aeb |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ab0ed5e872804293ad7dab7125234aeb2025-01-09T11:44:46ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202410432A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer ImmunotherapyBin Ren0Sihua Yan1Zongheng Li2Ya Huang3Haobin Cai4Jing Yang5Qingdeng Fan6Chunmei Chen7Fanchao Que8Guochao Wu9Lin Huang10Ruilong Zhou11Jiaoyang Zhu12Chenggong Yan13Gang Liu14Zheyu Shen15Shipeng Ning16School of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaDepartment of Breast Surgery The Second Affiliated Hospital of Guangxi Medical University Nanning 530000 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaMedical Imaging Center Nanfang Hospital Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen Fujian 361102 ChinaSchool of Biomedical Engineering Southern Medical University 1023 Shatai South Road Guangzhou Guangdong 510515 ChinaDepartment of Breast Surgery The Second Affiliated Hospital of Guangxi Medical University Nanning 530000 ChinaAbstract To overcome the problems of Gd‐based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo‐charging system‐like GBCA is designed and constructed for magnetic resonance imaging (MRI) guided STING pathway‐activated cancer immunotherapy. Poly(acrylic acid) (PAA) is used to coordinate with Gd3+, forming a Gd/PAA macrochelate. Both Gd/PAA macrochelate and SR717 are conjugated to cystamine (CA) to obtain SR717‐CA@Gd/PAA self‐assembled nanoparticles (SAN), which are termed as Turbo S because of its similarity with the Turbo‐charging system of cars. After accumulation in tumors and internalization in tumor cells, the disulfide linkage in Turbo S undergoes a cleavage process catalyzed by glutathione (GSH), leading to the release of Gd/PAA and SR717. The released Gd/PAA gain a high r1 value (17.11 mM−1 s−1 at 7.0 T; 57.81 mM−1 s−1 at 3.0 T), indicating its strong T1 imaging capability. Turbo S with a low dosage of SR717 (8.9 mg kg−1) achieved a higher tumor immunotherapeutic efficacy than free SR717 with a high dosage (30 mg kg−1). The excellent delivery efficiency, high tumor treatment efficacy, and superior biosafety demonstrate that the Turbo S can be used as a promising candidate for tumor immunotherapy.https://doi.org/10.1002/advs.202410432cancer immunotherapyGd‐based contrast agents (GBCAs)magnetic resonance imaging (MRI)stimulator of interferon genes (STING)turbo‐charging system‐like contrast agent (Turbo S) |
| spellingShingle | Bin Ren Sihua Yan Zongheng Li Ya Huang Haobin Cai Jing Yang Qingdeng Fan Chunmei Chen Fanchao Que Guochao Wu Lin Huang Ruilong Zhou Jiaoyang Zhu Chenggong Yan Gang Liu Zheyu Shen Shipeng Ning A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy Advanced Science cancer immunotherapy Gd‐based contrast agents (GBCAs) magnetic resonance imaging (MRI) stimulator of interferon genes (STING) turbo‐charging system‐like contrast agent (Turbo S) |
| title | A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy |
| title_full | A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy |
| title_fullStr | A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy |
| title_full_unstemmed | A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy |
| title_short | A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy |
| title_sort | turbo charging system like contrast agent for mri guided sting pathway activated cancer immunotherapy |
| topic | cancer immunotherapy Gd‐based contrast agents (GBCAs) magnetic resonance imaging (MRI) stimulator of interferon genes (STING) turbo‐charging system‐like contrast agent (Turbo S) |
| url | https://doi.org/10.1002/advs.202410432 |
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