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

Autor: Huang Z; 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., Wang Y; 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., Su C; School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000, China., Li W; Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715, China., Wu M; Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038, China., Li W; College of Bioengineering, Chongqing University, Chongqing, 400044, China., Wu J; School of medical imaging, North Sichuan Medical College, Nanchong, Sichuan, 637000, China., Xia Q; 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., He H; 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.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Apr; Vol. 20 (15), pp. e2306912. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1002/smll.202306912
Abstrakt: 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 Mn 2+ , 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.
(© 2023 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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