The rapid clearance of intravenously administered nanoparticles (NPs) from the bloodstream is a major unsolved problem in nanomedicine. Here, we describe the first use of biocompatible protein-avoidant ionic liquids (PAILs) as NP surface modifiers to reduce opsonization. An ionic liquid choline hexenoate, selected for its aversion to serum proteins, was used to stably coat the surface of poly(lactic-co-glycolic acid) (PLGA) NPs. Compared with bare PLGA and poly(ethylene glycol)–coated PLGA particles, the PAIL-PLGA NPs showed resistance to protein adsorption in vitro and greater retention in blood of mice at 24 hours. Choline hexenoate redirected biodistribution of NPs, with preferential accumulation in the lungs with 50% of the administered dose accumulating in the lungs and <5% in the liver. Lung accumulation was attributed to spontaneous attachment of the PAIL-coated NPs on red blood cells in vivo. Overall, ionic liquids are a promising class of materials for NP modification for biomedical applications.

从血液中快速清除静脉内给药的纳米颗粒 (NPs) 是纳米医学中一个尚未解决的主要问题。在这里，我们描述了首次使用生物相容性蛋白质避免离子液体 (PAIL) 作为 NP 表面改性剂来减少调理作用。一种离子液体己烯酸胆碱，因其对血清蛋白的厌恶而被选择，用于稳定地包被聚乳酸-co-乙醇酸) (PLGA) NPs。与裸露的 PLGA 和聚（乙二醇）包覆的 PLGA 颗粒相比，PAIL-PLGA NPs 在体外表现出对蛋白质吸附的抵抗力，并且在 24 小时后在小鼠血液中的保留能力更强。己烯酸胆碱重定向 NPs 的生物分布，优先在肺中积累，50% 的给药剂量在肺中积累，<5% 在肝脏中。肺积聚归因于 PAIL 包被的 NPs 在体内红细胞上的自发附着。总体而言，离子液体是用于生物医学应用的 NP 改性的一类有前途的材料。