Mn-Anti-CTLA4-CREKA-Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy
Zixuan Huang
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240 China
Search for more papers by this authorCorresponding Author
Yejing Wang
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCan Su
School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000 China
Search for more papers by this authorWanting Li
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Search for more papers by this authorMin Wu
Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038 China
Search for more papers by this authorWuling Li
College of Bioengineering, Chongqing University, Chongqing, 400044 China
Search for more papers by this authorCorresponding Author
Jun Wu
School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorQingyou Xia
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Huawei He
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorZixuan Huang
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240 China
Search for more papers by this authorCorresponding Author
Yejing Wang
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCan Su
School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000 China
Search for more papers by this authorWanting Li
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Search for more papers by this authorMin Wu
Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038 China
Search for more papers by this authorWuling Li
College of Bioengineering, Chongqing University, Chongqing, 400044 China
Search for more papers by this authorCorresponding Author
Jun Wu
School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorQingyou Xia
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Huawei He
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715 China
Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorAbstract
The integration of magnetic resonance imaging (MRI), cGAS-STING, and anti-CTLA-4 (aCTLA-4) based immunotherapy offers new opportunities for tumor precision therapy. However, the precise delivery of aCTLA-4 and manganese (Mn), an activator of cGAS, to tumors remains a major challenge for enhanced MRI and active immunotherapy. Herein, a theragnostic nanosphere Mn-CREKA-aCTLA-4-SS (MCCS) is prepared by covalently assembling Mn2+, silk sericin (SS), pentapeptide CREKA, and aCTLA-4. MCCS are stable with an average size of 160 nm and is almost negatively charged or neutral at pH 5.5/7.4. T1-weighted images showed MCCS actively targeted tumors to improve the relaxation rate r1 and contrast time of MRI. This studies demonstrated MCCS raises reactive oxygen species levels, activates the cGAS-STING pathway, stimulates effectors CD8+ and CD80+ T cells, reduces regulatory T cell numbers, and increases IFN-γ and granzyme secretion, thereby inducing tumor cells autophagy and apoptosis in vitro and in vivo. Also, MCCS are biocompatible and biosafe. These studies show the great potential of Mn-/SS-based integrative material MCCS for precision and personalized tumor nanotheragnostics.
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 in the supplementary material of this article.
Supporting Information
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| smll202306912-sup-0001-SuppMat.pdf1.4 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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