Nanomedicine Lab, Faculty of Biology, Medicine & Health, AV Hill Building, University of Manchester, Manchester Academic Healthy Science Centre, Manchester, M13 9PT, UK.
Laboratory for Lipidomics and Lipid Biology, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester Academic Healthy Science Centre, Manchester, M13 9PT, UK.
Nanoscale. 2023 Jul 6;15(26):11038-11051. doi: 10.1039/d2nr05982g.
The spontaneous self-assembly of biomolecules around the surface of nanoparticles (NPs) once exposed to plasma and other biofluids, has been termed the 'biomolecule corona'. While the protein composition of the biomolecule corona has been widely characterised, the interaction of NPs with the plasma lipidome has not been fully investigated. Here, we use targeted and untargeted lipidomics to analyse a wide spectrum of bioactive lipids adsorbed onto the surface of liposome NPs post-incubation with human plasma. Our data indicate that the biomolecule corona contains a diverse mixture of simple and complex lipid species, including sphingolipids such as ceramides and sphingomyelins, glycerolipids, glycerophospholipids, cholesteryl esters, as well as oxylipin and -acyl ethanolamine derivatives of fatty acids. Although the corona lipidomic profiles reflected the overall composition of the plasma lipidome, monohydroxy- and oxo-fatty acid oxylipins, mono-, di- and tri- acylglycerols, sphingomyelins and ceramides showed a preferential binding for liposome NP surface. Interestingly, the biomolecule corona lipid profiles appeared to mirror those of the lipoprotein lipid cargo, suggesting that lipid species may be carried within the lipoprotein complexes attached to the corona. Proteomic analysis of corona-associated proteins showed the presence of several apolipoproteins (A-I, A-II, A-IV, B, C-I, C-III, C-IV, C2-C4, D, E, L, M and lipoprotein Lp(A)), supporting this notion. Our findings reveal the wide lipid diversity of the biomolecule corona and indicate a potential lipoprotein-mediated adsorption mechanism of lipids onto liposome NPs, highlighting the importance of bridging proteomics with lipidomics to fully comprehend the interactions at the bio-nano interface.
纳米粒子（NPs）表面一旦暴露于等离子体和其他生物流体中，生物分子会自发组装，这被称为“生物分子冠”。虽然生物分子冠的蛋白质组成已经得到广泛描述，但 NP 与血浆脂类组的相互作用尚未得到充分研究。在这里，我们使用靶向和非靶向脂质组学来分析脂质体 NP 与人类血浆孵育后吸附在表面的广泛谱生物活性脂质。我们的数据表明，生物分子冠含有多种简单和复杂的脂质种类，包括神经酰胺和鞘磷脂等鞘脂、甘油酯、甘油磷脂、胆固醇酯，以及氧代脂和脂肪酸的酰基乙醇胺衍生物。尽管冠层脂质组学图谱反映了血浆脂类组的总体组成，但单羟基和氧代脂肪酸氧代脂、单酰基、二酰基和三酰基甘油、鞘磷脂和神经酰胺优先与脂质体 NP 表面结合。有趣的是，生物分子冠的脂质谱似乎反映了脂蛋白脂质货物的脂质谱，这表明脂质种类可能存在于与冠相连的脂蛋白复合物中。对冠相关蛋白的蛋白质组学分析表明存在几种载脂蛋白（A-I、A-II、A-IV、B、C-I、C-III、C-IV、C2-C4、D、E、L、M 和脂蛋白 Lp（A）），支持了这一观点。我们的发现揭示了生物分子冠的广泛脂质多样性，并表明了脂质通过脂蛋白介导吸附到脂质体 NP 的潜在机制，强调了将蛋白质组学与脂质组学相结合以全面理解生物-纳米界面相互作用的重要性。
