کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5032935 1370002 2017 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells
ترجمه فارسی عنوان
تحویل اسید لاکتیک-گلوکولیک اسید از دیسولفیرام به سلول های ساقه مانند سرطان کبد منتقل می شود
موضوعات مرتبط
مهندسی و علوم پایه سایر رشته های مهندسی مهندسی پزشکی
چکیده انگلیسی

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.

Graphical AbstractDisulfiram (DS), an antialcoholism drug, shows very strong anticancer activity in vitro but no encouraging clinical data published. This discrepancy is caused by the very short (<4 min) half-life of DS in the bloodstream.DS is a strong divalent copper(II) chelator. The reaction between DS and copper(II) generates reactive oxygen species (ROS) which target cancer cells. In this reaction, the intact sulfhydryl groups in DS molecule are essential. After oral administration of DS, the sulfhydryl groups are promptly methylated or glucuronidated in portal vein and liver. The methylated and glucuronidated DS completely loses its anticancer activity. In this study, we developed an intravenously applicable long-circulating PLGA encapsulated DS (DS-PLGA). DS-PLGA extends the half-life of DS to 7 h and delivers intact DS to cancer tissues where it reacts with copper to generate ROS targeting cancer cells.342

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 13, Issue 2, February 2017, Pages 641-657
نویسندگان
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