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
相关论文
共 42 条
[21]   Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging [J].
Li, Xiaojie ;
Qian, Yinfeng ;
Liu, Tao ;
Hu, Xianglong ;
Zhang, Guoying ;
You, Yezi ;
Liu, Shiyong .
BIOMATERIALS, 2011, 32 (27) :6595-6605
[22]   cRGD-functionalized polymer micelles for targeted doxorubicin delivery [J].
Nasongkla, N ;
Shuai, X ;
Ai, H ;
Weinberg, BD ;
Pink, J ;
Boothman, DA ;
Gao, JM .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (46) :6323-6327
[23]   Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release [J].
Oerlemans, Chris ;
Bult, Wouter ;
Bos, Mariska ;
Storm, Gert ;
Nijsen, J. Frank W. ;
Hennink, Wim E. .
PHARMACEUTICAL RESEARCH, 2010, 27 (12) :2569-2589
[24]   Quantitative and reversible lectin-induced association of gold nanoparticles modified with α-lactosyl-ω-mercapto-poly(ethylene glycol) [J].
Otsuka, H ;
Akiyama, Y ;
Nagasaki, Y ;
Kataoka, K .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (34) :8226-8230
[25]   Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles [J].
Owens, DE ;
Peppas, NA .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2006, 307 (01) :93-102
[26]   Cooperative Nanoparticles for Tumor Detection and Photothermally Triggered Drug Delivery [J].
Park, Ji-Ho ;
von Maltzahn, Geoffrey ;
Ong, Luvena L. ;
Centrone, Andrea ;
Hatton, T. Alan ;
Ruoslahti, Erkki ;
Bhatia, Sangeeta N. ;
Sailor, Michael J. .
ADVANCED MATERIALS, 2010, 22 (08) :880-+
[27]   Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery [J].
Prabaharan, Mani ;
Grailer, Jamison J. ;
Pilla, Srikanth ;
Steeber, Douglas A. ;
Gong, Shaoqin .
BIOMATERIALS, 2009, 30 (29) :5757-5766
[28]   Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(L-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery [J].
Prabaharan, Mani ;
Grailer, Jamison J. ;
Pilla, Srikanth ;
Steeber, Douglas A. ;
Gong, Shaoqin .
BIOMATERIALS, 2009, 30 (16) :3009-3019
[29]   Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems [J].
Tacar, Oktay ;
Sriamornsak, Pornsak ;
Dass, Crispin R. .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2013, 65 (02) :157-170
[30]   Micellar nanocarriers: Pharmaceutical perspectives [J].
Torchilin, V. P. .
PHARMACEUTICAL RESEARCH, 2007, 24 (01) :1-16