Self-Cascade Nanozyme Reactor as a Cuproptosis Inducer Synergistic Inhibition of Cellular Respiration Boosting Radioimmunotherapy.

Autor: Li R; Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430000, China.; Department of Respiratory Intervention, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Jinshui, Zhengzhou, 450008, China., Zhao W; Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430000, China., Han Z; Department of General Surgery, Tangdu Hospital, the Air Force Medical University, Xi'an, 710000, China., Feng N; Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Wu T; Nanozyme Medical Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450001, China.; Department of Pharmacy of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 450001, China., Xiong H; Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430000, China., Jiang W; Nanozyme Medical Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450001, China.; Department of Pharmacy of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 450001, China.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Jun; Vol. 20 (25), pp. e2306263. Date of Electronic Publication: 2024 Jan 14.
DOI: 10.1002/smll.202306263
Abstrakt: Intrinsic or acquired radioresistance remained an important challenge in the successful management of cancer. Herein, a novel "smart" multifunctional copper-based nanocomposite (RCL@Pd@CuZ) to improve radiotherapy (RT) sensitivity is designed and developed. In this nanoplatform, DSPE-PEG-RGD modified on the liposome surface enhanced tumor targeting and permeability; capsaicin inserted into the phospholipid bilayer improved the hypoxic conditions in the tumor microenvironment (TME) by inhibiting mitochondrial respiration; a Cu MOF porous cube encapsulated in liposome generated highly active hydroxyl radicals (OH·), consumed GSH and promoted cuproptosis by releasing Cu 2+ ; the ultrasmall palladium (Pd) nanozyme within the cubes exhibited peroxidase activity, catalyzing toxic OH· generation and releasing oxygen from hydrogen peroxide; and lastly, Pd, as an element with a relatively high atomic number (Z) enhanced the photoelectric and Compton effects of X-rays. Therefore, RCL@Pd@CuZ enhance RT sensitivity by ameliorating hypoxia, promoting cuproptosis, depleting GSH, amplifying oxidative stress, and enhancing X-ray absorption  , consequently potently magnifying immunogenic cell death (ICD). In a mouse model , RCL@Pd@CuZ combined with RT yielded >90% inhibition compared with that obtained by RT alone in addition to a greater quantity of DC maturation and CD8 + T cell infiltration. This nanoplatform offered a promising remedial modality to facilitate cuproptosis-related cancer radioimmunotherapy.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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