https://scholars.lib.ntu.edu.tw/handle/123456789/637504
標題: | Macrophage-Hitchhiked Orally Administered β-Glucans-Functionalized Nanoparticles as "Precision-Guided Stealth Missiles" for Targeted Pancreatic Cancer Therapy | 作者: | Chen, Kuan-Hung Nguyen, Nhien Huang, Tun-Yu Lin, Yu-Jung Yu, Yu-Tzu HSIANG-LIN SONG Wang, Jui-To Nguyen, Van Khanh Chen, Hsin-Lung Chu, Li-An Chiang, Hui-Hua Kenny Sung, Hsing-Wen |
關鍵字: | desmoplastic stromal barrier; immune checkpoint blockade; intestinal epithelial barrier; macrophage hitchhiking; tumor microenvironment | 公開日期: | 十月-2023 | 卷: | 35 | 期: | 40 | 來源出版物: | Advanced materials (Deerfield Beach, Fla.) | 摘要: | 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-ZnD@Mϕ). 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637504 | ISSN: | 09359648 | DOI: | 10.1002/adma.202304735 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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