Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy.
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.
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Wenjun
W
Li
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Cuifang
C
Zheng
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Zhengyin
Z
Pan
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Chi
C
Chen
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Dehong
D
Hu
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; Paul-Drude-Institut für Festkörperelektronik, Hausvogteiplatz 5-7, 10117, Berlin, Germany.
Guanhui
G
Gao
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Shendong
S
Kang
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Haodong
H
Cui
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Ping
P
Gong
Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China. Electronic address: lt.cai@siat.ac.cn.
Lintao
L
Cai
D000818:Animals; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000627:therapeutic use; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000378:metabolism / Q000627:therapeutic use*; D061848:Optical Imaging / Q000379:methods; D061088:Photoacoustic Techniques / Q000379:methods; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000627:therapeutic use*; D011166:Porphyrins / Q000378:metabolism / Q000627:therapeutic use*; D000068936:Theranostic Nanomedicine / Q000379:methods*
D002735:Chlorophyllides; D008823:Micelles; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase
Chlorin e6 (Ce6); Dual-model tumor imaging; Hyaluronan (HA); Hyaluronidase-actived; Photodynamic therapy; Theranostic nanoparticles