抗辐射性
NADPH氧化酶
CD44细胞
活性氧
癌症研究
癌细胞
放射治疗
癌症
下调和上调
透明质酸
DNA损伤
化学
肿瘤微环境
黑色素瘤
细胞生长
细胞
医学
生物化学
内科学
DNA
解剖
基因
肿瘤细胞
作者
Lei Zhu,Yi Zhao,Tongrui Liu,Minglong Chen,Wei Qian,Bing‐Hua Jiang,Benjamin G Barwick,Lumeng Zhang,Toncred M. Styblo,Xiaoxian Li,Lily Yang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-10-18
卷期号:16 (11): 18708-18728
被引量:15
标识
DOI:10.1021/acsnano.2c07440
摘要
Upregulation of NADPH oxidases (NOXs) in cancer cells leads to chronic increase in intracellular reactive oxygen species (ROS) and adaptation to a high ROS level for cell survival and, thereby, low sensitivity to radiotherapy. To overcome resistance to radiotherapy, we have developed a bioactive and CD44 targeted hyaluronic acid nanoparticle encapsulated with an NOX inhibitor, GKT831 (HANP/GKT831). We found that HANP/GKT831 had stronger inhibitory effects on ROS generation and cell proliferation than that of GKT831 alone in cancer cells. Systemic delivery of HANP/GKT831 led to the targeted accumulation in breast cancer patient derived xenograft (PDX) tumors in nude mice. Importantly, the combination of systemic delivery of HANP/GKT831 with a low dose of local radiotherapy significantly enhanced tumor growth inhibition in breast cancer PDX models. Our results showed that HANP/GKT831 primed tumor cells to radiation-induced DNA damage and cell death by downregulation of DNA repair function and oncogenic signal pathways.
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