Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma

Guido Costamagna, Byoung-Chan Bae, Su-Geun Yang, Seok Jeong, Don Haeng Lee, Kun Na, Joon Mee Kim, Richard A. Kozarek, Hiroyuki Isayama, Jacques Deviere, Dong Wan Seo, D. Nageshwar Reddy

Risultato della ricerca: Contributo in rivistaArticolo in rivista

19 Citazioni (Scopus)

Abstract

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma.
Lingua originaleEnglish
pagine (da-a)8487-8495
Numero di pagine9
RivistaBiomaterials
Volume35
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Bile duct stent
  • Cholangiocarcinoma
  • Membrane-covered self-expanding metal stent (SEMS)
  • Pheophorbide A
  • Photodynamic therapy

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