An Immunocompetent Hafnium Oxide-Based STING Nanoagonist for Cancer Radio-immunotherapy.

Autor: Cao Y; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Ding S; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Hu Y; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Zeng L; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Zhou J; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Lin L; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Zhang X; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Ma Q; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Cai R; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Zhang Y; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Duan G; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China., Bian XW; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China.; Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing 401329, P. R. China., Tian G; Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology Ministry of Education of China, Chongqing 400038, P. R. China.; Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing 401329, P. R. China.
Jazyk: angličtina
Zdroj: ACS nano [ACS Nano] 2024 Feb 06; Vol. 18 (5), pp. 4189-4204. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1021/acsnano.3c09293
Abstrakt: cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO 2 ) core and the manganese oxide (MnO 2 ) shell. HfO 2 -mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO 2 sustainably releases Mn 2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn 2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.
Databáze: MEDLINE