Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines
Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines
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DOI：
10.1126/sciadv.abb8133
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发表时间：
2020-06-01
期刊：
影响因子：
13.6
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Dirisala, Anjaneyulu;Uchida, Satoshi;Kataoka, Kazunori
全身施用纳米药物的一个主要关键问题是肝窦内皮的非特异性清除，导致纳米药物进入靶组织的递送效率大幅下降。在这里，我们通过使用线性或双臂聚乙二醇（PEG）缀合寡聚（L-赖氨酸）（OligoLys）对肝血窦进行原位隐形涂层来解决这个问题。 PEG-OligoLys 选择性地附着在肝窦上进行 PEG 涂层，使其他组织的内皮未被涂层，因此纳米药物可接近。此外，具有双臂PEG构型的OligoLys最终从肝窦壁清除到胆汁，而具有线性PEG的OligoLys持续存在于肝窦壁中，可能导致肝脏生理功能的长期紊乱。这种双臂-PEG-OligoLys对肝窦的瞬时和选择性隐形涂层可有效防止分别代表合成和天然纳米药物的非病毒和病毒基因载体的肝窦清除，从而提高其在靶组织中的基因转染效率。
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.