Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy

被引:108
作者
Li, Wenjun [1 ]
Zheng, Cuifang [1 ]
Pan, Zhengyin [1 ]
Chen, Chi [1 ]
Hu, Dehong [1 ]
Gao, Guanhui [1 ,2 ]
Kang, Shendong [1 ]
Cui, Haodong [1 ]
Gong, Ping [1 ]
Cai, Lintao [1 ]
机构
[1] Chinese Acad Sci, Shenzhen Inst Adv Technol, CAS Key Lab Hlth Informat, Guangdong Key Lab Nanomed, Shenzhen 518055, Peoples R China
[2] Paul Drude Inst Festkorperelekt, Hausvogteipl 5-7, D-10117 Berlin, Germany
基金
中国国家自然科学基金;
关键词
Theranostic nanoparticles; Hyaluronidase-actived; Dual-model tumor imaging; Chlorin e6 (Ce6); Hyaluronan (HA); Photodynamic therapy; PHOTOTHERMAL THERAPY; GRAPHENE OXIDE; GOLD NANOSTARS; CHLORIN E6; CANCER; ACID; NANOPARTICLES; NANOGELS; CELLS; NANOCLUSTERS;
D O I
10.1016/j.biomaterials.2016.05.019
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
We here report smart hyaluronidase-actived theranostic nanoparticles based on hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA-ADH-Ce6 conjugates and self assembling into HACE NPs. The resulting nanoparticles showed stable nano-structure in aqueous condition with uniform size distribution and can be actively disassembled in the presence of hyaluronidase (over-expressed in tumor cells), exhibiting hyaluronidase-responsive "OFF/ON" behavior of fluorescence signal. The HACE NPs were rapidly taken up to human lung cancer cells A549 via CD44 (the HA receptor on the surface of tumor cells) receptor mediated endocytosis. Upon laser irradiation, the HACE NPs realized good near-infrared fluorescence imaging and photoacoustic imaging in the tumor bearing mice, which showed 5-fold higher fluorescence intensity and 3-fold higher photoacoustic (PA) intensity than free Ce6, respectively. In addition, under low dose of laser power, the HACE NPs presented more effective photodynamic therapy to suppression of tumor growth than free Ce6 in vitro and in vivo. Overall, these results suggest that the well-defined HACE NPs is a biocompatible theranostic nanoplatform for in vivo dual-modal tumor imaging and phototherapy simultaneously. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:10 / 19
页数:10
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