Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles

Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles

© 2020 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 32(2020), 47 vom: 21. Nov., Seite e2004853
1. Verfasser: Rao, Lang (VerfasserIn)
Weitere Verfasser: Zhao, Shu-Kun, Wen, Churan, Tian, Rui, Lin, Lisen, Cai, Bo, Sun, Yue, Kang, Fei, Yang, Zhen, He, Liangcan, Mu, Jing, Meng, Qian-Fang, Yao, Guangyu, Xie, Ni, Chen, Xiaoyuan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CD47-SIRPα cancer immunotherapy cell-membrane coatings gene engineering macrophage immune response tumor-associated macrophages
Beschreibung
Zusammenfassung:© 2020 Wiley-VCH GmbH.
Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy
Beschreibung:Date Completed 12.08.2021
Date Revised 10.10.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202004853