中性粒细胞胞外陷阱
阿霉素
转移
癌症研究
体内
化疗
癌症
细胞外
乳腺癌
体外
细胞毒性
化学
医学
生物
免疫学
炎症
内科学
生物化学
生物技术
作者
Yongwei Hao,Xue Li,Yuefei Liu,Dalin Liu,Xuehan Zhao,Shenglu Ji,Hongli Chen,Yaojia Li
标识
DOI:10.1016/j.cej.2023.142957
摘要
New treatment patterns have emerged by destroying neutrophil extracellular traps (NETs) with DNase-1 to prevent tumor metastasis. However, the DNase-1 as a therapeutic agent has short half-life in blood plasma and low potency to kill tumor owing to the intrinsically intricate tumor microenvironment. Herein, a manganese-enriched nanosystem (DMMnSiO3-PEG/DOX/DNase-1) has been developed to inhibit lung metastasis of breast cancer by delivering doxorubicin and DNase-1 for degrading neutrophil extracellular traps and improving chemotherapy therapy synergistically. Specifically, this PEG-modified nanosystem can not only accumulate at the site of tumor tissue but also be captured by NETs. In tumor site, DOX were released from this nanosystem in response to a lower pH and higher GSH to facilitate apoptosis effect of tumor cells efficiently with the help of DNase-1. Then, those remaining nanoparticles were captured by NETs to disassemble them and the released Mn2+ as the cofactor of DNase-1 could increase the NETs lyse. In all, that nanosystem has been proven to inhibit tumor growth by a chemotherapeutic effect and suppresses distant metastasis by disassembling NETs through in vitro and in vivo evaluations. This strategy demonstrates immense potential to provide an effective and safe therapeutic regimen for the treatment in patients with metastatic breast cancer.
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