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      Active Transportation of Liposome Enhances Tumor Accumulation, Penetration, and Therapeutic Efficacy.

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          Abstract

          Liposomes are the first and mostly explored nanocarriers for cancer drug delivery, which have shown great promise in clinical applications, but their limited accumulation and penetration into the tumor interstitial space, significantly reduce the therapeutic efficacy. Here, a γ-glutamyltranspeptidase (GGT)-triggered charge-switchable approach is reported that can trigger the fast endocytosis and transcytosis of the liposome in tumor microenvironments to overcome the harsh biological barriers in tumor tissues. The active transporting liposomal nanocarrier (GCSDL) is prepared by surface modification with a glutathione (GSH) moiety and encapsulated with doxorubicin (DOX). When the GCSDL contacts with tumor vascular endothelial cells, the overexpressed GGT enzyme on cytomembrane catalyzes the hydrolysis of GSH to generate cationic primary amines. The cationic GCSDL triggers fast caveolae-mediated endocytosis and vesicle-mediated transcytosis, resulting in sequential transcytosis to augment its tumor accumulation and penetration. Along with continual intercellular transportation, GCSDL can release DOX throughout the tumor to induce cancer cell apoptosis, resulting in complete eradication of hepatocellular carcinoma and cessation of pancreatic ductal adenocarcinoma's progression. This study develops an efficient strategy to realize high tumor accumulation and deep penetration for the liposomal drug delivery system via active transcytosis.

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          Author and article information

          Journal
          Small
          Small (Weinheim an der Bergstrasse, Germany)
          Wiley
          1613-6829
          1613-6810
          November 2020
          : 16
          : 44
          Affiliations
          [1 ] Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.
          [2 ] Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
          [3 ] Department of Pathology, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
          [4 ] ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, 311215, China.
          Article
          10.1002/smll.202004172
          33030305
          4119f93c-074e-479e-992d-2d7153796b0e
          History

          transcytosis,cancer drug delivery,γ-glutamyltranspeptidase,tumor accumulation and penetration,liposome

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