Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor
Duo Wang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorTianqi Nie
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorCuiqing Huang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorZerong Chen
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorXiaocong Ma
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorWeiming Fang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorCorresponding Author
Yanyu Huang
Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA, 95817 USA
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Liangping Luo
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, 510317 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zeyu Xiao
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorDuo Wang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorTianqi Nie
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorCuiqing Huang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorZerong Chen
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorXiaocong Ma
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorWeiming Fang
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Search for more papers by this authorCorresponding Author
Yanyu Huang
Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA, 95817 USA
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Liangping Luo
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, 510317 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zeyu Xiao
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorAbstract
Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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