纳米载体
活性氧
阿霉素
多重耐药
细胞内
过氧化氢
癌细胞
流出
细胞凋亡
化学
生物物理学
药物输送
材料科学
生物化学
纳米技术
生物
癌症
化疗
抗生素
遗传学
作者
Ranjith Kumar Kankala,Chenguang Liu,Shibin Wang,Pei‐Yao Xu,Lokesh Kumar Mende,Chen‐Lun Liu,Chia‐Hung Lee,Yufang Hu
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2017-09-22
卷期号:3 (10): 2431-2442
被引量:132
标识
DOI:10.1021/acsbiomaterials.7b00569
摘要
Recently, multidrug resistance (MDR) has become a major clinical chemotherapeutic burden that robustly diminishes the intracellular drug levels through various mechanisms. To overcome the doxorubicin (Dox) resistance in tumor cells, we designed a hierarchical nanohybrid system possessing copper-substituted mesoporous silica nanoparticles (Cu-MSNs). Further, Dox was conjugated to copper metal in the Cu-MSNs framework through a pH-sensitive coordination link, which is acutely sensitive to the tumor acidic environment (pH 5.0–6.0). In the end, the nanocarrier was coated with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), a P-gp inhibitor-entrenched compact liposome net for obstructing the drug efflux pump. Copper ions in the framework synergize the antitumor activity of Dox by enhancing the intracellular reactive oxygen species (ROS) levels through a Fenton-like reaction-mediated conversion of hydrogen peroxide. Furthermore, intracellularly generated ROS triggered the apoptosis by reducing the cellular as well as mitochondrial membrane integrity in MDR cells, which was confirmed by the mitochondrial membrane potential (MMP) measurement. The advancement of the design and critical improvement of cytotoxic properties through free radical attack demonstrate that the proposed hierarchical design can devastate the MDR for efficient cancer treatment.
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