Filamentous, Mixed Micelles of Triblock Copolymers Enhance Tumor Localization of Indocyanine Green in a Murine Xenograft Model

被引:42
作者
Kim, Tae Hee [1 ]
Mount, Christopher W. [1 ]
Dulken, Benjamin W. [1 ]
Ramos, Jenelyn [3 ]
Fu, Caroline J. [3 ]
Khant, Htet A. [3 ]
Chiu, Wah [3 ]
Gombotz, Wayne R. [2 ]
Pun, Suzie H. [1 ]
机构
[1] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[2] Omeros Corp, Seattle, WA 98101 USA
[3] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA
关键词
filamentous micelles; indocyanine green; tumor delivery; triblock copolymers; BIODEGRADABLE AMPHIPHILIC POLY(ETHYLENE; DRUG-DELIVERY; BLOCK-COPOLYMERS; DIBLOCK COPOLYMERS; AQUEOUS-SOLUTION; MICELLIZATION PHENOMENA; MULTIDRUG-RESISTANCE; POLYMERIC MICELLES; DOXORUBICIN; OXIDE);
D O I
10.1021/mp200381c
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles composed of poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by noninvasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability were attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components.
引用
收藏
页码:135 / 143
页数:9
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