药品
前药
顺铂
抗药性
缺氧(环境)
肿瘤微环境
材料科学
纳米医学
透明质酸
肿瘤缺氧
药理学
癌症研究
医学
化疗
肿瘤细胞
生物
氧气
纳米技术
化学
纳米颗粒
内科学
放射治疗
有机化学
微生物学
遗传学
作者
Yi Liu,Dong Wang,Yinchu Ma,Jiaxiang Dou,Wei Jiang,Li Wang,Qin Wang,Shuya Li,Yucai Wang,Min Li
出处
期刊:Biomaterials
[Elsevier]
日期:2023-03-01
卷期号:294: 122023-122023
被引量:8
标识
DOI:10.1016/j.biomaterials.2023.122023
摘要
Tumor hypoxia heterogeneity, a hallmark of the tumor microenvironment, confers resistance to conventional chemotherapy due to insufficient drug availability and drug sensitivity in hypoxic regions. To overcome these challenges, we develope a nanomedicine, NPHPaPN, constructed with hyaluronic acid (HA) grafted with cisplatin prodrug and PEG-azobenzene for hypoxia-responsive PEG shell deshielding and loaded with a DNA damage repair inhibitor (NERi). After arriving at the tumor site, NPHPaPN deshields the PEG shell in response to hypoxia due to the enzymolysis of azobenzene and thus exposes HA. The exposed HA binds to the highly expressed CD44 on cisplatin-resistant tumor cells and mediates drug internalization, thus increasing drug availability to hypoxic tumor cells. After intracellular hyaluronidase-mediated cleavage, the HA NPs release the cisplatin prodrug and NERi, and cause enhanced DNA damage and consequent cell death, thus enhancing the drug sensitivity of hypoxic tumor cells. Eventually, NPHPaPN achieves distinct tumor growth suppression with an ∼84.4% inhibition rate.
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