Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I : C) promote melanoma regression
Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I : C) promote melanoma regression
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ferumoxytol 与 TLR3 激动剂聚 (I:C) 结合或表面功能化可激活抗肿瘤巨噬细胞，促进黑色素瘤消退
DOI：
10.7150/thno.29746
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发表时间：
2018-11
期刊：
影响因子：
12.4
通讯作者：
Hou Yayi
中科院分区：
文献类型：
--
作者：
Zhao Jiaojiao;Zhang Zhengkui;Xue Yaxian;Wang Guoqun;Cheng Yuan;Pan Yuchen;Zhao Shuli;Hou Yayi
Macrophages orchestrate inflammation and control the promotion or inhibition of tumors and metastasis. Ferumoxytol (FMT), a clinically approved iron oxide nanoparticle, possesses anti-tumor therapeutic potential by inducing pro-inflammatory macrophage polarization. Toll-like receptor 3 (TLR3) activation also potently enhances the anti-tumor response of immune cells. Herein, the anti-tumor potential of macrophages harnessed by FMT combined with the TLR3 agonist, poly (I:C) (PIC), and FP-NPs (nanoparticles composed of amino-modified FMT (FMT-NH2) surface functionalized with PIC) was explored. Methods: Proliferation of B16F10 cells co-cultured with macrophages was measured using immunofluorescence or flow cytometry (FCM). Phagocytosis was analyzed using FCM and fluorescence imaging. FP-NPs were prepared through electrostatic interactions and their properties were characterized using dynamic light scattering, transmission electron microscopy, and gel retardation assay. Anti-tumor and anti-metastasis effects were evaluated in B16F10 tumor-bearing mice, and tumor-infiltrating immunocytes were detected by immunofluorescence staining and FCM. Results: FMT, PIC, or the combination of both hardly impaired B16F10 cell viability. However, FMT combined with PIC synergistically inhibited their proliferation by shifting macrophages to a tumoricidal phenotype with upregulated TNF-alpha and iNOS, increased NO secretion and augmented phagocytosis induced by NOX2-derived ROS in vitro. Combined treatment with FMT/PIC and FMT-NH2/PIC respectively resulted in primary melanoma regression and alleviated pulmonary metastasis with elevated pro-inflammatory macrophage infiltration and upregulation of pro-inflammatory genes in vivo. In comparison, FP-NPs with properties of internalization by macrophages and accumulation in the lung produced a more pronounced anti-metastatic effect accompanied with decreased myeloid-derived suppressor cells, and tumor-associated macrophages shifted to M1 phenotype. In vitro mechanistic studies revealed that FP-NPs nanoparticles barely affected B1 6F10 cell viability, but specifically retarded their growth by steering macrophages to M1 phenotype through NF-kappa B signaling. Conclusion: FMT synergized with the TLR3 agonist PIC either in combination or as a nano-composition to induce macrophage activation for primary and metastatic melanoma regression, and the nano-composition of FP-NPs exhibited a more superior anti-metastatic efficacy.
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影响因子：
38.3
作者：
通讯作者：
--
影响因子：
10.1
作者：
Karla R. Wiehagen;N. Girgis;Douglas H. Yamada;Andressa A. Smith;S. Chan;I. Grewal;M. Quigley;R. Verona
通讯作者：
Karla R. Wiehagen;N. Girgis;Douglas H. Yamada;Andressa A. Smith;S. Chan;I. Grewal;M. Quigley;R. Verona
影响因子：
14
作者：
Shi, Jinjin;Yu, Xiaoyuan;Zhang, Zhenzhong
通讯作者：
Zhang, Zhenzhong
影响因子：
2
作者：
Yanhong Sun;Jun Li;Yi Zhang;Y. Tu;Changzheng Huang;J. Tao;Ming-Wei Yang;Liu Yang
通讯作者：
Yanhong Sun;Jun Li;Yi Zhang;Y. Tu;Changzheng Huang;J. Tao;Ming-Wei Yang;Liu Yang
DOI：
10.1073/pnas.1113744109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Cortez-Retamozo, Virna;Etzrodt, Martin;Pittet, Mikael J.
通讯作者：
Pittet, Mikael J.