pH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

被引：124
作者：
Chen, Ching-Yi [1 ]
Kim, Tae Hee [2 ]
Wu, Wen-Chung [1 ]
Huang, Chi-Ming [3 ]
Wei, Hua [2 ]
Mount, Christopher W. [2 ]
Tian, Yanqing [1 ]
Jang, Sei-Hum [1 ]
Pun, Suzie H. [2 ]
Jen, Alex K. -Y. [1 ]
机构：
[1] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA
[2] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[3] Natl Cheng Kung Univ, Dept Chem Engn, Tainan 70101, Taiwan
来源：
BIOMATERIALS | 2013年 / 34卷 / 18期
关键词：
Polymeric micelle; Temperature sensitive; Anti-cancer; pH-sensitive; Tumor delivery; TRANSFER RADICAL POLYMERIZATION; BLOCK-COPOLYMER MICELLES; CORE-SHELL NANOPARTICLES; MURINE XENOGRAFT MODEL; VASCULAR-PERMEABILITY; TRIBLOCK COPOLYMERS; ANTITUMOR EFFICACY; CONTROLLED-RELEASE; DOXORUBICIN; CARRIERS;
D O I：
10.1016/j.biomaterials.2013.02.049
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(epsilon-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (similar to 7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4501 / 4509
页数：9
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