Nebulized Immunotherapy of Orthotopic Lung Cancer by Mild Magnetothermal-Based Innate Immunity Activations.

Autor: Chen L; School of Chemical Science and Engineering, Institute of Advanced Study, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 200092, Shanghai, P.R. China., Hu P; School of Chemical Science and Engineering, Institute of Advanced Study, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 200092, Shanghai, P.R. China.; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 200050, Shanghai, P.R. China., Fang W; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 200050, Shanghai, P.R. China., Wu T; School of Chemical Science and Engineering, Institute of Advanced Study, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 200092, Shanghai, P.R. China., Shi J; School of Chemical Science and Engineering, Institute of Advanced Study, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 200092, Shanghai, P.R. China.; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 200050, Shanghai, P.R. China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Sep 29, pp. e202413127. Date of Electronic Publication: 2024 Sep 29.
DOI: 10.1002/anie.202413127
Abstrakt: Advances in adaptive immunity have greatly contributed to the development of cancer immunotherapy. However, its over-low efficacy and insufficient invasion of immune cells in the tumor tissue, and safety problems caused by cytokine storm, have seriously impeded further clinical application for solid tumor immunotherapy. Notably, the immune microenvironment of the lungs is naturally enriched with alveolar macrophages (AMs). Herein, we introduce a novel nebulized magnetothermal immunotherapy strategy to treat orthotopic lung cancer by using magnetothermal nanomaterial (Zn-CoFe 2 O 4 @Zn-MnFe 2 O 4 -PEG, named ZCMP), which can release iron ions via an acid/thermal-catalytic reaction to maximize the use of lung's immune environment through the cascade activations of AMs and natural killer (NK) cells. Nebulized administration greatly enhance drug bioavailability by localized drug accumulation at the lesion site. Upon mild magnetic hyperthermia, the released iron ions catalyze endogenous H 2 O 2 decomposition to produce reactive oxygen species (ROS), which triggers the M1 polarization of AMs, and the resultant inflammatory cytokine IFN-β, IL-1β and IL-15 releases to activate c-Jun, STAT5 and GZMB related signaling pathways, promoting NK cells proliferation and activation. This innovative strategy optimally utilizes the lung's immune environment and shows excellent immunotherapeutic outcomes against orthotopic lung cancer.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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