DACHPt-Loaded Nanoparticles Self-assembled from Biodegradable Dendritic Copolymer Polyglutamic Acid-b-D-α-Tocopheryl Polyethylene Glycol 1000 Succinate for Multidrug Resistant Lung Cancer Therapy

被引：15
|
作者：
Tsai, Hsiang-I [1 ]
Jiang, Lijuan [1 ]
Zeng, Xiaowei [2 ]
Chen, Hongbo [2 ]
Li, Zihuang [3 ]
Cheng, Wei [4 ]
Zhang, Jinxie [1 ]
Pan, Jie [5 ]
Wan, Dong [5 ]
Gao, Li [6 ]
Xie, Zhenhua [4 ]
Huang, Laiqiang [1 ,4 ]
Mei, Lin [2 ]
Liu, Gan [2 ]
机构：
[1] Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
[2] Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Guangzhou, Guangdong, Peoples R China
[3] Jinan Univ, Dept Radiat Oncol, Shenzhen Municipal Peoples Hosp, Clin Med Coll 2, Shenzhen, Peoples R China
[4] Tsinghua Univ, Grad Sch Shenzhen, Div Life & Hlth Sci, Shenzhen, Peoples R China
[5] Tianjin Polytech Univ, Sch Environm & Chem Engn, Tianjin, Peoples R China
[6] Guilin Med Univ, Dept Urol, Affiliated Hosp, Guilin, Peoples R China
来源：
FRONTIERS IN PHARMACOLOGY | 2018年 / 9卷
基金：
中国国家自然科学基金;
关键词：
multidrug resistance; TPGS; dendritic copolymers; nanoparticles; DACHPt; VITAMIN-E TPGS; PLGA NANOPARTICLES; P-GLYCOPROTEIN; DRUG-DELIVERY; CISPLATIN; INHIBITION; RELEASE; NANOCARRIERS; CHEMOTHERAPY; MICELLES;
D O I：
10.3389/fphar.2018.00119
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid-b-D-alpha -tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-b-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.
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页数：10
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