Encapsulated mitochondria to reprogram the metabolism of M2-type macrophages for anti-tumor therapy

: Wang, Yonghui; Liu, Chang; Ma, Xiaodong; Filppula, Anne; Cui, Youbin; Ye, Jiangbin; Zhang, Hongbo

Publisher: Royal Society of Chemistry (RSC)

: 2024

: Nanoscale

: 16

: 45

: 20925

: 20939

: 2040-3364

: 2040-3372

DOI: https://doi.org/10.1039/D4NR02471K

: https://doi.org/10.1039/D4NR02471K

: https://research.utu.fi/converis/portal/detail/Publication/459074334

M2-type macrophages (M2Φ) play a pro-tumorigenic role and are closely associated with tumor development, where metabolic dysregulation exacerbates the immunosuppressive tumor microenvironment and fosters tumor growth. Mitochondria serve as the regulatory center of cellular metabolism, yet effective methods to modulate M2Φ mitochondria within the tumor microenvironment remain lacking. In this study, we developed a technique utilizing the bio-encapsulation of mitochondria in Zeolitic Imidazolate Framework-8 (ZiF-8), referred to as Mito@ZiF-8. Our findings demonstrated that this coating protects intact mitochondria and preserves their bioactivity over an extended period after isolation. We successfully delivered Mito@ZiF-8 into M2Φ, which inhibited the secretion of pro-inflammatory factors, promoted the release of anti-inflammatory factors, and reprogrammed M2Φ metabolism. This innovative approach has the potential to reduce breast cancer cell metastasis and enhance sensitivity to chemotherapy drugs such as 6-thioguanine, cisplatin, and doxorubicin (Dox). Mito@ZiF-8 aims to reprogram the M2Φ microenvironment to support anti-tumor therapies, offering a novel strategy for improving the effectiveness of breast cancer treatment.

d4nr02471k.pdf

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We gratefully acknowledge the financial support provided by various sources, including the Academy of Finland through the Research Fellowship (Grant No. 328933), Research Project (Grant No. 347897), Health Profile Solutions (Grant No. 336355), and the InFLAMES Flagship (Grant No. 337531). We are also thankful for the funding from the Finland-China Food and Health International Pilot Project, supported by the Finnish Ministry of Education and Culture, as well as the China Scholarship Council. In addition, we express our sincere appreciation to the First Hospital of Jilin University for their collaboration and valuable contributions. We further extend our thanks to the Turku Bioscience Centre for facilitating access to advanced infrastructure, including Electron Microscopy, Confocal, and Flow Cytometry, which were essential for sample analysis, and to the Turku Metabolomics Centre for providing comprehensive sample analysis services.