Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self-Assembled Metal-Phenolic Network Nanoparticles
Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self-Assembled Metal-Phenolic Network Nanoparticles
复制标题
自组装金属-酚醛网络纳米颗粒的有毒活性氧增强协同组合疗法
DOI：
10.1002/adma.201704877
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发表时间：
2018-02-22
影响因子：
29.4
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Dai, Yunlu;Yang, Zhen;Chen, Xiaoyuan
工程功能纳米材料以其高效的治疗效果和最小的副作用日益成为治疗癌症的一种有前途的策略。本论文通过生物相容的金属-多酚网络自组装技术，将多柔比星(DOX)和铂前药包埋在纳米粒中，设计了一种ROS增强的联合化疗平台。DOX和白金药物都可以激活烟酰胺腺嘌呤二核苷酸磷酸氧化酶，产生超氧自由基(O-2(中心点-))。多酚类超氧化物歧化酶活性可以催化O-2(中心圆点-)生成H_2O_2。最后，Fenton反应生成剧毒的Ho中心点自由基。Ros Ho中心点可以通过一连串的生物反应来协同化疗。正电子发射断层成像的正电子发射断层成像所制备的DOX@铂前药Fe3+纳米粒(DPPF NPs)显示血液循环延长和高肿瘤积聚。此外，DPPF纳米粒能有效抑制肿瘤生长，减少抗癌药物的副作用。本研究建立了一种新型的ROS促进的肿瘤治疗协同纳米药物平台。
Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal-polyphenol networks self-assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O-2(center dot-)). The superoxide dismutase-like activity of polyphenols can catalyze H2O2 generation from O-2(center dot-). Finally, the highly toxic HO center dot free radicals are generated by a Fenton reaction. The ROS HO center dot can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of Zr-89-labeled as-prepared DOX@Pt prodrug Fe3+ nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy.