Acidity-Triggered Tumor-Targeted Nanosystem for Synergistic Therapy via a Cascade of ROS Generation and NO Release

被引:64
作者
Cao, Yufei [1 ]
Liu, Mingsheng [1 ]
Cheng, Ju [2 ]
Yin, Juanjuan [1 ]
Huang, Congshu [3 ]
Cui, Haiyan [1 ]
Zhang, Xiangdong [1 ]
Zhao, Guanghui [1 ]
机构
[1] Lanzhou Univ, Inst Biochem Engn & Environm Technol, State Key Lab Appl Organ Chem, Coll Chem & Chem Engn, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Peoples R China
[3] Luoyang Ship Mat Res Inst, State Key Lab Marine Corros & Protect, Xiamen 361011, Peoples R China
基金
中国国家自然科学基金;
关键词
nitric oxide; ROS; arginine; cancer therapy; charge-reversal; ENHANCED PHOTODYNAMIC THERAPY; NITRIC-OXIDE; HYDROGEN-PEROXIDE; CO RELEASE; NANOPARTICLES; LIGHT; DERIVATIVES; MECHANISMS; COMPOSITE; DELIVERY;
D O I
10.1021/acsami.0c04791
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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. beta-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, center dot OH is generated from H2O2, and the ONOO- could be generated from an interaction between center dot O-2(-) (generated through the Haber-Weiss reaction) and NO. Arg-rich poly(e-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.
引用
收藏
页码:28975 / 28984
页数:10
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