Synthesis of cholic acid-core poly(ε-caprolactone-ran-lactide)-b-poly(ethylene glycol) 1000 random copolymer as a chemotherapeutic nanocarrier for liver cancer treatment

被引：39

作者：

Tao, Wei ^{[1
,2
,3
]}

Zeng, Xiaowei ^{[1
,2
,3
]}

Zhang, Jinxie ^{[1
,2
,3
]}

Zhu, Huijun ^{[1
,2
,3
]}

Chang, Danfeng ^{[2
,3
,4
]}

Zhang, Xudong ^{[1
,2
,3
]}

Gao, Yongfeng ^{[1
,2
,3
]}

Tang, Jiao ^{[5
]}

Huang, Laiqiang ^{[1
,2
,3
]}

Mei, Lin ^{[1
,2
,3
]}

机构：

[1] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Minist Prov Jointly Constructed Base State Key La, Shenzhen Key Lab Chem Biol, Shenzhen Key Lab Gene & Antibody Therapy, Shenzhen 518055, Peoples R China

[3] Tsinghua Univ, Grad Sch Shenzhen, Div Life & Hlth Sci, Shenzhen 518055, Peoples R China

[4] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

[5] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China

来源：

BIOMATERIALS SCIENCE | 2014年 / 2卷 / 09期

基金：

中国国家自然科学基金;

关键词：

DOCETAXEL-LOADED NANOPARTICLES; STAR-SHAPED POLYMER; DRUG-DELIVERY; CELLULAR INTERNALIZATION; BLOCK-COPOLYMERS; IN-VITRO; DIBLOCK COPOLYMER; PEG; STABILITY; MICELLES;

D O I：

10.1039/c4bm00134f

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

A star-shaped random copolymer, cholic acid functionalized poly(e-caprolactone-ran-lactide)-b-poly-(ethylene glycol) 1000 (CA-(PCL-ran-PLA)-b-PEG(1k)), was synthesized by a core-first approach involving three stages of chemical reactions, and was characterized by hydrogen-1 nuclear magnetic resonance (H-1 NMR), gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded nanoparticles (NPs) were prepared by a modified nano-precipitation method. The formation and characterization of these NPs were confirmed through dynamic light scattering, zeta potential measurements, field emission scanning electron microscopy, and transmission electron microscopy. The in vitro release profiles indicated that CA-(PCL-ran-PLA)-b-PEG(1k) NPs had excellent sustained and controlled drug release properties. Both confocal laser scanning microscope and flow cytometric results showed that the coumarin-6 loaded CA-(PCL-ran-PLA)-b-PEG(1k) NPs had the highest cellular uptake efficiency compared with PEG(1k)-b-(PCL-ran-PLA) NPs and CA-(PCL-ran-PLA) NPs in human hepatic carcinoma cells. The docetaxel-loaded CA-(PCL-ran-PLA)-b-PEG(1k) NPs were also proved to have the highest drug loading content, encapsulation efficiency, and the best anti-tumor efficacy both in vitro and in vivo. In conclusion, the star-shaped CA-(PCL-ran-PLA)-b-PEG(1k) copolymer was successfully synthesized and could be used as a promising drug-loaded biomaterial for liver cancer chemotherapy.

引用

页码：1262 / 1274

页数：13