Mn‐Anti‐CTLA4‐CREKA‐Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy

Author:

Huang Zixuan123,Wang Yejing12,Su Can4,Li Wanting1,Wu Min5,Li Wuling6,Wu Jun4,Xia Qingyou12,He Huawei12ORCID

Affiliation:

1. Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center Southwest University Chongqing 400715 China

2. 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

3. School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China

4. School of medical imaging North Sichuan Medical College Nanchong Sichuan 637000 China

5. Department of Stem Cell and Regenerative Medicine Southwest Hospital, Army Medical University Chongqing 400038 China

6. College of Bioengineering Chongqing University Chongqing 400044 China

Abstract

AbstractThe 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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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