Multi-functional self-fluorescent unimolecular micelles for tumor-targeted drug delivery and bioimaging

被引:95
作者
Chen, Guojun [1 ,2 ]
Wang, Liwei [2 ,3 ]
Cordie, Travis [3 ]
Vokoun, Corinne [4 ]
Eliceiri, Kevin W. [4 ]
Gong, Shaoqin [1 ,2 ,3 ,5 ]
机构
[1] Univ Wisconsin, Mat Sci Program, Madison, WI 53715 USA
[2] Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI 53715 USA
[3] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53715 USA
[4] Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI 53715 USA
[5] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53715 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Self-fluorescence; Unimolecular micelles; Drug nanocarrier; Drug delivery; Bioimaging probe; Cancer theranostics; QUANTUM DOTS; CANCER-THERAPY; INTEGRIN ALPHA(V)BETA(3); NANOPARTICLES; NANOCARRIERS; DOXORUBICIN; PHOTOLUMINESCENT; CYTOTOXICITY; SYSTEMS;
D O I
10.1016/j.biomaterials.2015.01.006
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
A novel type of self-fluorescent unimolecular micelle nanoparticle (NP) formed by multi-arm star amphiphilic block copolymer, Boltron(R) H40 (H40, a 4th generation hyperbranched polymer)-biodegradable photo-luminescent polymer (BPLP)-poly(ethylene glycol) (PEG) conjugated with cRGD peptide (i.e., H40-BPLP-PEG-cRGD) was designed, synthesized, and characterized. The hydrophobic BPLP segment was self-fluorescent, thereby making the unimolecular micelle NP self-fluorescent. cRGD peptides, which can effectively target alpha(v)beta(3) integrin-expressing tumor neovasculature and tumor cells, were selectively conjugated onto the surface of the micelles to offer active tumor-targeting ability. This unique self-fluorescent unimolecular micelle exhibited excellent photostability and low cytotoxicity, making it an attractive bioimaging probe for NP tracking for a variety of microscopy techniques including fluorescent microscopy, confocal laser scanning microscopy (CLSM), and two-photon microscopy. Moreover, this self-fluorescent unimolecular micelle NP also demonstrated excellent stability in aqueous solutions due to its covalent nature, high drug loading level, pH-controlled drug release, and passive and active tumor-targeting abilities, thereby making it a promising nanoplatform for targeted cancer theranostics. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:41 / 50
页数:10
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