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Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance
Yu, Qingsong1; Wei, Zhenke2; Shi, Jiyun3; Guan, Shuli1; Du, Nan1; Shen, Tong1; Tang, Hao1; Jia, Bing3; Wang, Fan3; Gan, Zhihua1,2
刊名BIOMACROMOLECULES
2015-09-01
DOI10.1021/acs.biomac.5b00460
16期:9页:2645-2655
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Chemistry, Organic ; Polymer Science
研究领域[WOS]Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
关键词[WOS]IN-VIVO ; GLOMERULAR-FILTRATION ; HPMA COPOLYMERS ; N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMERS ; TUMOR ACCUMULATION ; BLOCK-COPOLYMERS ; DRUG-DELIVERY ; TOMOGRAPHY ; CANCER ; THERAPEUTICS
英文摘要

Well-defined water-soluble block copolymers poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine) (PEG-b-P (HPMA-co-MAGG)) and their doxorubicin (Dox) conjugates with different composition and molecular weight were synthesized. These Dox conjugates can form micelles in buffer solution. The physicochemical properties, in vivo biodistribution, blood clearance, and especially the tumor accumulation of copolymers and micelles were studied. Severe liver accumulation can be observed for PEG-b-PMAGG copolymers. This was quite different from their Dox conjugate for which decreased RES uptake and elevated kidney accumulation could be observed. When decrease the negative charge to an appropriate amount such as 8-10 mol %, both RES uptake and kidney accumulation could be suppressed. Obvious tumor accumulation could be achieved especially when the molecular weight were increased from similar to 40 to similar to 80 KDa. These results provided us with a guideline for the design of nanoscaled drug delivery system as well as a potential option for treating kidney-related cancers.

语种英语
WOS记录号WOS:000361341700010
项目编号51390481 ; 51025314 ; 50873109 ; 81472412 ; 30930030 ; 2015M570919
资助机构National Natural Science Foundations of China ; China Postdoctoral Foundation ; Ministry of Finance ; Ministry of Education of PRC
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58824
专题北京大学医药卫生分析中心
北京大学基础医学院
作者单位1.Beijing Univ Chem Technol, State Key Lab Organ Inorgan Composites, Beijing Lab Biomed Mat, Coll Life Sci & Technol, Beijing 100029, Peoples R China
2.Chinese Acad Sci, Inst Chem, CAS Key Lab Engn Plast, Beijing 100190, Peoples R China
3.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
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GB/T 7714
Yu, Qingsong,Wei, Zhenke,Shi, Jiyun,et al. Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance[J]. BIOMACROMOLECULES,2015,16(9):2645-2655.
APA Yu, Qingsong.,Wei, Zhenke.,Shi, Jiyun.,Guan, Shuli.,Du, Nan.,...&Gan, Zhihua.(2015).Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance.BIOMACROMOLECULES,16(9),2645-2655.
MLA Yu, Qingsong,et al."Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance".BIOMACROMOLECULES 16.9(2015):2645-2655.
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