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Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy

Authors
Yoon, Hong YeolKoo, HeebeomChoi, Ki YoungLee, So JinKim, KwangmeyungKwon, Ick ChanLeary, James F.Park, KinamYuk, Soon HongPark, Jae HyungChoi, Kuiwon
Issue Date
5월-2012
Publisher
ELSEVIER SCI LTD
Keywords
Photodynamic therapy; Imaging; Tumor-targeting; Nanoparticle; Hyaluronic acid; Chlorin e6
Citation
BIOMATERIALS, v.33, no.15, pp.3980 - 3989
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
33
Number
15
Start Page
3980
End Page
3989
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/108610
DOI
10.1016/j.biomaterials.2012.02.016
ISSN
0142-9612
Abstract
Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5 beta-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded hyaluronic acid nanoparticles (Ce6-HANP5), wherein in the loading efficiency of Ce6 was higher than 80%. The resulting Ce6-HANP5 showed stable nano-structure in aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may enable intracellular release of Ce6 at the tumor tissue. After an intravenous injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the tumor tissue via the passive targeting mechanism and specifically enter tumor cells through the receptor-mediated endocytosis based on the interactions between HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon laser irradiation, Ce6 which was released from the nanoparticles could generate fluorescence and singlet oxygen inside tumor cells, resulting in effective suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously. (C) 2012 Elsevier Ltd. All rights reserved.
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