表面粗糙度会影响糖基化纳米颗粒的蛋白质冠形成,并改变它们的细胞摄取。
Surface roughness influences the protein corona formation of glycosylated nanoparticles and alter their cellular uptake.
机构信息
Centre for Advanced Macromolecular Design, School of Chemistry, University of New South Wales UNSW, Sydney, Australia.
School of Biomedical Engineering, University of New South Wales UNSW, Sydney, Australia.
出版信息
Nanoscale. 2019 Dec 28;11(48):23259-23267. doi: 10.1039/c9nr06835j. Epub 2019 Nov 29.
Recently the role of protein absorption in nanoparticle drug delivery has gathered significant attention as the protein corona can significantly decide on the fate of nanoparticles in the body. Although it is known that the surface chemistry will significantly influence the amount and type of bound protein, there is little known about the effect of surface roughness and surface topography on the interaction. In this work, we show how patchy nanoparticles can noticeably reduce the adsorption of proteins compared to spherical nanoparticles with a smooth surface as demonstrated using six ABC triblock terpolymers based on glucose, mannose and galactose. To obtain patchy nanoparticles, poly(2-d-sugar ethyl acrylate)-b-poly (n-butyl acrylate)-b-poly(4-vinyl pyridine) (PSugEA-b-PBuA-b-P4VP) was prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization and assembled into nanoparticles with a patch-like appearance and a hydrodynamic diameter of around 130-160 nm. As control, smooth nanoparticles were prepared from poly(2-d-sugar ethyl acrylate)-b-poly (n-butyl acrylate)-b-polystyrene (PSugEA-b-PBuA-b-PS). The patchy nanoparticles displayed significantly reduced protein absorption when exposed to serum-supplemented cell culture media, as observed using dynamic light scattering. The smooth particles, however, supported the formation of a large protein corona. Additionally, an enrichment of haemoglobin was observed in the corona compared to the serum protein in solution. The amount of albumin on the surface was observed to be dependent on the type of sugar with glucose resulting in the highest absorption. The protein corona led to cellular uptake that was unrelated to the underlying sugar, which was supposed to help targeting specific cell lines. This example demonstrated how the protein corona can override any attempts to target receptor expressing cells.
最近,蛋白质吸收在纳米颗粒药物输送中的作用引起了人们的极大关注,因为蛋白质冠可以显著决定纳米颗粒在体内的命运。虽然已经知道表面化学会显著影响结合蛋白的数量和类型,但对于表面粗糙度和形貌对相互作用的影响知之甚少。在这项工作中,我们展示了如何通过使用基于葡萄糖、甘露糖和半乳糖的六个 ABC 三嵌段共聚物,使具有粗糙表面的嵌段纳米颗粒与具有光滑表面的球形纳米颗粒相比,可以明显减少蛋白质的吸附。为了获得嵌段纳米颗粒,通过可逆加成-断裂链转移(RAFT)聚合制备了聚(2-二糖乙酯基丙烯酸酯)-b-聚(正丁基丙烯酸酯)-b-聚(4-乙烯基吡啶)(PSugEA-b-PBuA-b-P4VP),并组装成具有类似斑块外观和大约 130-160nm 的水动力直径的纳米颗粒。作为对照,从聚(2-二糖乙酯基丙烯酸酯)-b-聚(正丁基丙烯酸酯)-b-聚苯乙烯(PSugEA-b-PBuA-b-PS)制备了光滑的纳米颗粒。当暴露于含有血清的细胞培养基中时,通过动态光散射观察到,嵌段纳米颗粒的蛋白质吸附明显减少。然而,光滑的颗粒支持了大蛋白质冠的形成。此外,与溶液中的血清蛋白相比,在冠层中观察到血红蛋白的富集。观察到表面上的白蛋白量取决于糖的类型,其中葡萄糖的吸收量最高。观察到表面上的白蛋白量取决于糖的类型,其中葡萄糖的吸收量最高。观察到表面上的白蛋白量取决于糖的类型,其中葡萄糖的吸收量最高。观察到表面上的白蛋白量取决于糖的类型,其中葡萄糖的吸收量最高。观察到表面上的白蛋白量取决于糖的类型,其中葡萄糖的吸收量最高。
蛋白质冠导致了与底层糖无关的细胞摄取,这应该有助于靶向特定的细胞系。这个例子表明了蛋白质冠如何可以覆盖任何针对表达受体的细胞的尝试。