オオサワ　シゲヒト   Oosawa Shigehito   大澤　重仁    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines
掲載誌名	正式名：Science advances. 略　 称：Sci Adv ISSNコード：23752548
掲載区分	国外
巻・号・頁	6(26),pp.1-11
総ページ数	11
著者・共著者	Anjaneyulu Dirisala, Satoshi Uchida, Kazuko Toh, Junjie Li, Shigehito Osawa, Theofilus A. Tockary, Xueying Liu, Saed Abbasi, Kotaro Hayashi, Yuki Mochida, Shigeto Fukushima, Hiroaki Kinoh, Kensuke Osada, Kazunori Kataoka
発行年月	2020/06/26
概要	A major critical issue in systemically administered nanomedicines is nonspecific clearance by the liver sinusoidal endothelium, causing a substantial decrease in the delivery efficiency of nanomedicines into the target tissues. Here, we addressed this issue by in situ stealth coating of liver sinusoids using linear or two-armed poly(ethylene glycol) (PEG)–conjugated oligo(l-lysine) (OligoLys). PEG-OligoLys selectively attached to liver sinusoids for PEG coating, leaving the endothelium of other tissues uncoated and, thus, accessible to the nanomedicines. Further-more, OligoLys having a two-armed PEG configuration was ultimately cleared from sinusoidal walls to the bile, while OligoLys with linear PEG persisted in the sinusoidal walls, possibly causing prolonged disturbance of liver physiological functions. Such transient and selective stealth coating of liver sinusoids by two-arm-PEG-OligoLys was effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, representatives of synthetic and nature-derived nanomedicines, respectively, thereby boosting their gene transfection efficiency in the tar-get tissues.
DOI	10.1126/sciadv.abb8133