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Acidity-Triggered Tumor-Targeted Nanosystem for Synergistic Therapy via a Cascade of ROS Generation and NO Release.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-06-05 , DOI: 10.1021/acsami.0c04791
Yufei Cao 1 , Mingsheng Liu 1 , Ju Cheng 2 , Juanjuan Yin 1 , Congshu Huang 3 , Haiyan Cui 1 , Xiangdong Zhang 1 , Guanghui Zhao 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-06-05 , DOI: 10.1021/acsami.0c04791
Yufei Cao 1 , Mingsheng Liu 1 , Ju Cheng 2 , Juanjuan Yin 1 , Congshu Huang 3 , Haiyan Cui 1 , Xiangdong Zhang 1 , Guanghui Zhao 1
Affiliation
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Nitric oxide (NO) gas therapy has aroused intense interest in recent years. l-Arginine (l-Arg) reacts with reactive oxygen species (ROS) in tumor cells to generate NO. This phenomenon represents an effective method for tumor therapy. However, endogenous ROS levels in most types of tumor cells cannot enable an effective reaction. β-Lapachone is generally used to increase H2O2, which can oxidize guanidine derivatives to form nitric oxide in tumor cells. In addition, based on the ferrocene (Fc)-catalyzed Fenton reaction, ·OH is generated from H2O2, and the ONOO– could be generated from an interaction between ·O2– (generated through the Haber–Weiss reaction) and NO. Arg-rich poly(ε-caprolactone) (PCL)-b-PArg, a macromolecular NO donor, was accurately synthesized to avoid premature l-Arg leakage during in vivo transport. In this design, the self-assembled PCL-b-PArg nanoparticles were dressed with the tumor-shreddable masking (PEG-b-PDMA, a negatively charged pH-sensitive hydrophilic diblock polymer), to prepare P-lapa-Fc nanoparticles and hide penetrative capability in the circulation. The experimental results confirmed that this synergistic therapy based on ROS and NO had a significant inhibitory effect on cancer cells, thereby providing new inspiration for NO gas treatment.
中文翻译：
通过串连的ROS生成和NO释放进行酸度触发的肿瘤靶向纳米系统进行协同治疗。
近年来，一氧化氮（NO）气体疗法引起了人们的浓厚兴趣。1-精氨酸（1 - Arg ）与肿瘤细胞中的活性氧（ROS）反应生成NO。这种现象代表了一种有效的肿瘤治疗方法。但是，大多数类型的肿瘤细胞中的内源性ROS水平无法实现有效的反应。β-拉帕酮通常用于增加H 2 O 2，H 2 O 2可以氧化胍衍生物在肿瘤细胞中形成一氧化氮。此外，基于所述二茂铁（Fc）的催化的芬顿反应，·OH选自H产生2 ö 2和ONOO -可从之间的相互作用而产生·O2 2 -（通过Haber-Weiss反应生成）和否。准确合成了富含Arg的聚（ε-己内酯）（PCL）-b-PArg，它是大分子NO供体，以避免体内运输过程中过早的1 -Arg泄漏。在此设计中，将自组装的PCL-b-PArg纳米颗粒与可切碎肿瘤的掩膜（PEG-b-PDMA，带负电的pH敏感的亲水性二嵌段聚合物）配合使用，以制备P-lapa-Fc纳米颗粒并隐藏流通能力。实验结果证实，这种基于ROS和NO的协同疗法对癌细胞具有明显的抑制作用，从而为NO气体治疗提供了新的启示。
更新日期：2020-07-01
中文翻译：
通过串连的ROS生成和NO释放进行酸度触发的肿瘤靶向纳米系统进行协同治疗。
近年来，一氧化氮（NO）气体疗法引起了人们的浓厚兴趣。1-精氨酸（1 - Arg ）与肿瘤细胞中的活性氧（ROS）反应生成NO。这种现象代表了一种有效的肿瘤治疗方法。但是，大多数类型的肿瘤细胞中的内源性ROS水平无法实现有效的反应。β-拉帕酮通常用于增加H 2 O 2，H 2 O 2可以氧化胍衍生物在肿瘤细胞中形成一氧化氮。此外，基于所述二茂铁（Fc）的催化的芬顿反应，·OH选自H产生2 ö 2和ONOO -可从之间的相互作用而产生·O2 2 -（通过Haber-Weiss反应生成）和否。准确合成了富含Arg的聚（ε-己内酯）（PCL）-b-PArg，它是大分子NO供体，以避免体内运输过程中过早的1 -Arg泄漏。在此设计中，将自组装的PCL-b-PArg纳米颗粒与可切碎肿瘤的掩膜（PEG-b-PDMA，带负电的pH敏感的亲水性二嵌段聚合物）配合使用，以制备P-lapa-Fc纳米颗粒并隐藏流通能力。实验结果证实，这种基于ROS和NO的协同疗法对癌细胞具有明显的抑制作用，从而为NO气体治疗提供了新的启示。
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