title: Cellular distribution of injected PLGA-nanoparticles in the liver.
abstract: The cellular fate of nanoparticles in the liver is not fully understood. Because the effectiveness and safety of nanoparticles in liver therapy depends on targeting nanoparticles to the right cell populations, this study aimed to determine a relative distribution of PLGA-nanoparticles (sizes 271±1.4 nm) among liver cells in vivo. We found that Kupffer cells were the major cells that took up nanoparticles, followed by liver sinusoidal endothelial cells and hepatic stellate cells. Nanoparticles were found in only 7% of hepatocytes. Depletion of Kupffer cells by clodronate liposomes increased nanoparticle retention in liver sinusoidal endothelial cells and hepatic stellate cells, but not in hepatocytes. It is importantly suggested that studies of drug-loaded nanoparticle delivery to the liver have to demonstrate not only uptake of nanoparticles by the target cell type but also non-uptake by other cell types to assess their effect as well as ensure their safety.
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: jinkyu820@knu.ac.kr.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: teruo_utsumi@yahoo.com.
authors.forename: Teruo
authors.initials: T
authors.lastname: Utsumi
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: young-eun.seo@yale.edu.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Seo
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: yang.deng.yd@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: The Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan. Electronic address: ayano113@cc.okayama-u.ac.jp.
authors.forename: Ayano
authors.initials: A
authors.lastname: Satoh
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: mark.saltzman@yale.edu.
authors.forename: William Mark
authors.initials: WM
authors.lastname: Saltzman
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: yasuko.iwakiri@yale.edu.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
mesh_terms: D016503:Drug Delivery Systems; D022781:Hepatocytes; D006801:Humans; D007728:Kupffer Cells; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Hepatic stellate cells; Hepatocytes; Kupffer cells; Liver sinusoidal endothelial cells; nanomedicine