title: Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.
abstract: Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine-p(API-l-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib-pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, Illinois 60611, United States.
authors.forename: Wooram
authors.initials: W
authors.lastname: Park
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, Illinois 60611, United States.
authors.forename: Jeane
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, Illinois 60611, United States.
authors.forename: Soojeong
authors.initials: S
authors.lastname: Cho
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea , Bucheon-si, Gyeonggi do 14662, Republic of Korea.
authors.forename: Sin-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, Illinois 60611, United States.|Robert H. Lurie Comprehensive Cancer Center , Chicago, Illinois 60611, United States.|Department of Biomedical Engineering, Department of Electrical Engineering and Computer Science, and International Institute of Nanotechnology, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larson
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea , Bucheon-si, Gyeonggi do 14662, Republic of Korea.
authors.forename: Kun
authors.initials: K
authors.lastname: Na
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, Illinois 60611, United States.|Robert H. Lurie Comprehensive Cancer Center , Chicago, Illinois 60611, United States.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D053761:Nanocomposites / Q000737:chemistry*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: hepatocellular carcinoma; image-guided therapy; iron oxide nanoparticles; nanocomposite microspheres; pH-responsive materials; sorafenib