NUS Graduate School for Integrative Sciences and Engineering , National University of Singapore, Centre for Life Sciences (CeLS) , 28 Medical Drive, #05-01 , Singapore 117456.
Department of Biomedical Engineering , National University of Singapore , 4 Engineering Drive 3, Engineering Block 4, #04-08 , Singapore 117583.
Bioconjug Chem. 2018 Nov 21;29(11):3923-3934. doi: 10.1021/acs.bioconjchem.8b00743. Epub 2018 Oct 29.
Significant progress in the characterization of protein corona has been made. However, insights on how the corona affects the aggregation of nanoparticles (NPs) and consequent biological identity are still lacking. Here, we examined how the corona formed from four major serum proteins, immunoglobulin G (IgG), fibrinogen (FBG), apolipoprotein A1 (ApoA1), and human serum albumin (HSA), over a range of concentrations affects the aggregation of gold NPs (AuNPs). We found that at physiological pH of 7.4, all four proteins aggregated the AuNPs at low concentrations but conferred colloidal stability at high concentrations due to the complete "corona coat" around individual AuNPs. Due to their immune-related functions, IgG and FBG aggregated the AuNPs to a greater extent compared to HSA and ApoA1 which were mostly involved in transport of small molecules. We then introduced the AuNP-corona formed from each protein into an acidic solution at pH 6.2 with high ionic concentration for up to 24 h as a model of the tumor microenvironment to examine for changes in their aggregation. We observed that protein corona formation sterically stabilized the AuNP-corona for all four proteins, resulting in a smaller increase in aggregation and size compared to citrate-capped AuNPs. This was especially true for corona formed at high protein:AuNP ratios. Our study therefore showed that the formation of a complete "corona coat" around NPs at sufficiently high protein:NP ratio was required for colloidal stability of designed NP systems in both physiological and cancer microenvironment to maintain efficiency and efficacy in cancer drug delivery.
在蛋白质冠层的特性描述方面已经取得了重大进展。然而，关于冠层如何影响纳米颗粒（NPs）的聚集以及随之而来的生物学特性的信息仍然缺乏。在这里，我们研究了在生理 pH 值 7.4 下，四种主要血清蛋白（免疫球蛋白 G（IgG）、纤维蛋白原（FBG）、载脂蛋白 A1（ApoA1）和人血清白蛋白（HSA））在一系列浓度下形成的冠层如何影响金纳米颗粒（AuNPs）的聚集。我们发现，在生理 pH 值 7.4 下，所有四种蛋白质在低浓度下都会使 AuNPs 聚集，但由于单个 AuNPs 周围完全形成了“冠层”，因此在高浓度下赋予了胶体稳定性。由于它们具有免疫相关的功能，与主要参与小分子运输的 HSA 和 ApoA1 相比，IgG 和 FBG 使 AuNPs 聚集的程度更大。然后，我们将每种蛋白质形成的 AuNP 冠层在 pH 值为 6.2 的酸性溶液中加入高离子浓度，持续 24 小时，作为肿瘤微环境的模型，以检查其聚集的变化。我们观察到，蛋白质冠层的形成在空间上稳定了 AuNP 冠层，与柠檬酸封端的 AuNPs 相比，所有四种蛋白质的 AuNP 聚集和粒径增加都较小。对于高蛋白：AuNP 比例形成的冠层尤其如此。因此，我们的研究表明，在生理和癌症微环境中，为了维持设计的 NP 系统在癌症药物输送中的效率和效果，需要在足够高的蛋白：NP 比例下，在 NPs 周围形成完整的“冠层”，以保持胶体稳定性。
