Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
Max Planck-VISTEC Partner Laboratory for Sustainable Materials, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong, 21210, Thailand.
Small. 2022 Jan;18(3):e2103138. doi: 10.1002/smll.202103138. Epub 2021 Nov 10.
Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-free quantitative liquid chromatography-mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature-dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperature-responsive materials is a suitable method for imparting stealth properties to nanocarriers for drug-delivery.
载脂蛋白是一类重要的蛋白质，因为它们为纳米颗粒提供了所谓的隐身效应。纳米载体的隐身效应导致免疫细胞的非特异性摄取减少，从而延长血液循环时间。本文提出了一种通过在人血浆中孵育纳米载体时调节温度来特异性结合载脂蛋白的新策略。这种特异性结合反过来又可以控制纳米颗粒的隐身行为。制备了具有明确的聚（N-异丙基丙烯酰胺）壳的纳米颗粒，在约 32°C 时表现出可逆的疏水性变化。通过无标记定量液相色谱-质谱法表明，在 25°C 时，纳米颗粒主要富含载脂蛋白 J（簇蛋白），而在 37°C 时富含载脂蛋白 A1 和载脂蛋白 E。发现蛋白质的温度依赖性结合会显著影响 RAW264.7 和 HeLa 细胞对纳米颗粒的摄取。这些发现表明，用温度响应材料对纳米颗粒进行功能化是赋予纳米载体药物递送隐身性能的一种合适方法。
