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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
15 Jun 2024
Accepted
22 Oct 2024
First published
23 Oct 2024
This article is Open Access
Creative Commons BY license

Nanoscale, 2024, Advance Article

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

Y. Wang, C. Liu, X. Ma, A. Filppula, Y. Cui, J. Ye and H. Zhang, Nanoscale, 2024, Advance Article , DOI: 10.1039/D4NR02471K

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