Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer

被引：43

作者：

Dai, Lin ^{[1
]}

Wang, Luying ^{[1
]}

Deng, Lihong ^{[1
]}

Liu, Jing ^{[1
]}

Lei, Jiandu ^{[1
]}

Li, Dan ^{[1
]}

He, Jing ^{[1
]}

机构：

[1] Beijing Forestry Univ, MOE Key Lab Wooden Mat Sci & Applicat, Beijing 100083, Peoples R China

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

中国国家自然科学基金;

关键词：

ANTIMALARIAL-DRUG; CARBON NANOTUBES; IN-VITRO; ARTEMISININ; DERIVATIVES; POLYESTERS; PEGYLATION; APOPTOSIS; GRAPHENE; DELIVERY;

D O I：

10.1038/srep05871

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 similar to 8.14 wt%), significantly good water-solubilities (82- similar to 163-fold of DHA), excellent in vitro anticancer activities (at concentrations >= 8 mu g/ml, showed only 15-20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- similar to 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application.

引用

页数：10

共 47 条

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