期刊
BIOMATERIALS
卷 266, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120429
关键词
Ferroptosis; Tumor microenvironment; ROS; TAFs; Breast cancer
资金
- National Natural Science Foundation of China [81972812]
A novel kind of nanoparticles modified with beta-cyclodextrin grafted heparin successfully inhibited breast cancer metastasis through a hybrid mechanism of intracellular ROS activation and extracellular modulation of tumor microenvironment. This approach combined the activation of ferroptosis pathway with the inhibition of TGF-beta signaling, leading to a satisfactory anti-tumor metastasis effect in in vivo experiments.
The normal chemotherapy only induces the intracellular apoptosis pathway to promote primary tumor cells death, while not inhibit tumor metastasis. Herein, we proposed a kind of heparanase (HPSE)-driven sequential released nanoparticles, which modified with beta-cyclodextrin (beta-CD) grafted heparin (NLC/H(D + F + S) NPs) co-loading with doxorubicin (DOX), ferrocene (Fc), and TGF-beta receptor inhibitor (SB431542). NLC/H(D + F + S) NPs successfully inhibited breast cancer metastasis by intracellular and extracellular hybrid mechanism. DOX and Fc loaded in NLC/H(D + F + S) NPs effectively enhanced intracellular ROS level to activate ferroptosis pathway, the enhanced ROS also induced the apoptosis pathway and decreased MMP-9 expression to synergize with ferroptosis for tumor therapy. In extracellular site, SB431542 was sequentially released by HPSE-driven, which blocked tumor metastasis by modulating tumor microenvironment, decreasing TAFs activation, and reducing the secretion of TGF-beta. In addition, anti-tumor immune response induced by ferroptosis further strengthened the effect of tumor therapy. Finally, under the help of intracellular and extracellular mechanisms launched by NLC/H(D + F + S) NPs, the satisfactory anti-tumor metastasis effect was obtained in the in vivo antitumor assays. Therefore, NLC/H(D + F + S) NPs was a novel dosage regimen for breast cancer therapy through intracellular and extracellular mechanisms, in which ferroptosis induced by ROS played an important role.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据