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Stent containing CD44-targeting polymeric prodrug nanoparticles that release paclitaxel and gemcitabine in a time interval-controlled manner for synergistic human biliary cancer therapy

 Dayeon Yun  ;  Hyun-Ouk Kim  ;  Hye Young Son  ;  Yuna Choi  ;  Ilkoo Noh  ;  Jong-Woo Lim  ;  Jihye Kim  ;  Haejin Chun  ;  Geunseon Park  ;  Dong Ki Lee  ;  Sung Il Jang  ;  Eunji Jang  ;  Yong-Min Huh  ;  Seungjoo Haam 
 Journal of Materials Chemistry B, Vol.5(31) : 6317-6324, 2017 
Journal Title
 Journal of Materials Chemistry B 
Issue Date
The use of drug-eluting stents (DESs) is a promising strategy for non-vascular diseases, especially human biliary cancer. However, the implementation of DESs suffers from two major obstacles: the side effects of drugs and the difficulty of controlling the drug release. These problems can be overcome if the stent elutes targeting nanoparticles that release drugs at time intervals that are dictated by the mechanisms of those drugs. We designed temporally controlled polymeric multi-prodrug nanoparticles (TCMPNs) that can be eluted from stents comprising polyurethane (PU) nanofiber as a polymeric matrix and paclitaxel (PTX)-loaded, CD44-targeting, hyaluronic acid-conjugated poly(lactic-co-glycolic acid) and gemcitabine (GEM) (P–H–G). TCMPNs enable two different types of drugs to be released temporally; PTX is released first owing to the collapse of the structure in the endosomes, and GEM, which induces synergistic anticancer activities, is hydrolyzed from P–H–G later in response to low pH. Embedded in the PU nanofiber, the TCMPNs demonstrate low initial burst behavior and sustainable release of the prodrug in vitro. Furthermore, TCMPN-eluting stents (TESs) exhibit continuous synergistic efficacy as available targeted cellular uptake prodrug delivery systems in tumor-bearing mice. These results demonstrate that this technology will open up cancer therapy by combining localized delivery and functional multi-drug-loaded nanoparticles.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
손혜영(Son, Hye Yeong) ORCID logo https://orcid.org/0000-0001-5977-6784
이동기(Lee, Dong Ki) ORCID logo https://orcid.org/0000-0002-0048-9112
허용민(Huh, Yong Min) ORCID logo https://orcid.org/0000-0002-9831-4475
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