Macrophage-Hitchhiked Orally Administered β-Glucans-Functionalized Nanoparticles as "Precision-Guided Stealth Missiles" for Targeted Pancreatic Cancer Therapy

Macrophage-Hitchhiked Orally Administered β-Glucans-Functionalized Nanoparticles as "Precision-Guided Stealth Missiles" for Targeted Pancreatic Cancer Therapy

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 40 vom: 15. Okt., Seite e2304735
1. Verfasser: Chen, Kuan-Hung (VerfasserIn)
Weitere Verfasser: Nguyen, Nhien, Huang, Tun-Yu, Lin, Yu-Jung, Yu, Yu-Tzu, Song, Hsiang-Lin, Wang, Jui-To, Nguyen, Van Khanh, Chen, Hsin-Lung, Chu, Li-An, Chiang, Hui-Hua Kenny, Sung, Hsing-Wen
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article desmoplastic stromal barrier immune checkpoint blockade intestinal epithelial barrier macrophage hitchhiking tumor microenvironment beta-Glucans
Beschreibung
Zusammenfassung:© 2023 Wiley-VCH GmbH.
The prognosis in cases of pancreatic ductal adenocarcinoma (PDAC) with current treatment modalities is poor owing to the highly desmoplastic tumor microenvironment (TME). Herein, a β-glucans-functionalized zinc-doxorubicin nanoparticle system (βGlus-ZnD NPs) that can be orally administered, is developed for targeted PDAC therapy. Following oral administration in PDAC-bearing mice, βGlus-ZnD NPs actively target/transpass microfold cells, overcome the intestinal epithelial barrier, and then undergo subsequent phagocytosis by endogenous macrophages (βGlus-ZnDMϕ). As hitchhiking cellular vehicles, βGlus-ZnD@Mϕ transits through the intestinal lymphatic system and enters systemic circulation, ultimately accumulating in the tumor tissue as a result of the tumor-homing and "stealth" properties that are conferred by endogenous Mϕ. Meanwhile, the Mϕ that hitchhikes βGlus-ZnD NPs is activated to produce matrix metalloproteinases, destroying the desmoplastic stromal barrier, and differentiates toward the M1 -like phenotype, modulating the TME and recruiting effector T cells, ultimately inducing apoptosis of the tumor cells. The combination of βGlus-ZnD@Mϕ and immune checkpoint blockade effectively inhibits the growth of the primary tumor and suppresses the development of metastasis. It thus represents an appealing approach to targeted PDAC therapy
Beschreibung:Date Completed 23.10.2023
Date Revised 13.12.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202304735