RT Journal Article
SR Electronic
T1 Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb8133
DO 10.1126/sciadv.abb8133
VO 6
IS 26
A1 Dirisala, Anjaneyulu
A1 Uchida, Satoshi
A1 Toh, Kazuko
A1 Li, Junjie
A1 Osawa, Shigehito
A1 Tockary, Theofilus A.
A1 Liu, Xueying
A1 Abbasi, Saed
A1 Hayashi, Kotaro
A1 Mochida, Yuki
A1 Fukushima, Shigeto
A1 Kinoh, Hiroaki
A1 Osada, Kensuke
A1 Kataoka, Kazunori
YR 2020
UL http://advances.sciencemag.org/content/6/26/eabb8133.abstract
AB 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. Furthermore, 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 target tissues.