@article{88bae91eb4984796892dfa9d4eea46e5,
title = "A multifunctional nanocarrier for efficient TRAIL-based gene therapy against hepatocellular carcinoma with desmoplasia in mice",
abstract = "The anticancer efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance. We developed a tumor-targeted LCPP (lipid/calcium/phosphate/protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells in a mouse model of HCC. TRAIL pDNA was encapsulated in a pH stimuli-responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, intracellular release of Ca2+ from the CaP core overcame TRAIL resistance by calcium influx-dependent DR5 up-regulation. TRAIL expression also attenuated fibrosis in liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. Conclusion: TRAIL pDNA delivered by HCC-targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL-based cancer therapy that could be developed for clinical applications. (Hepatology 2018;67:899–913).",
author = "Liu, {Chun Hung} and Chern, {Guann Jen} and Hsu, {Fu Fei} and Huang, {Kuan Wei} and Sung, {Yun Chieh} and Huang, {Hsi Chien} and Qiu, {Jiantai Timothy} and Wang, {Sheng Kai} and Lin, {Chu Chi} and Wu, {Chien Hsun} and Wu, {Han Chung} and Liu, {Jia Yu} and Yunching Chen",
note = "Funding Information: Received February 7, 2017; accepted September 1, 2017. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.29513/suppinfo. Supported by Ministry of Science and Technology (MOST; 104-2628-B-007-001-MY3, 105-2628-E-007-007-MY3), by Chang Gung Memorial Hospital-National Tsing Hua University Joint Research Grant (104N2744E1), by Chang Gung Memorial Hospital (CMRPG3E1281~2, CORPG3F0141~2, CMRPG3F0181) and by the National Institute for Health Research (NHRI-EX106-10609BC). *These authors contributed equally to this work. Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29513 Publisher Copyright: {\textcopyright} 2017 by the American Association for the Study of Liver Diseases.",
year = "2018",
month = mar,
doi = "10.1002/hep.29513",
language = "English",
volume = "67",
pages = "899--913",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "3",
}
