Maity Avijit, Bagchi Debanjan, De Soumya Kanti, Chakraborty Anjan
Department of Chemistry, Indian Institute of Technology Indore, Indore 453552, Madhya Pradesh, India.
Langmuir. 2023 Apr 11;39(14):4881-4894. doi: 10.1021/acs.langmuir.2c03077. Epub 2023 Mar 29.
The aggregation and subsequent precipitation of gold nanoparticles (Au NPs) in the presence of protein molecules restrict the usefulness of NPs in biomedical applications. Till now, the influence of different properties of Au NPs (size, surface charge, surface coatings) and proteins (surface charge, chemical modification, folded and unfolded states) and pH and ionic strength of the solution on the aggregation of both Au NPs and proteins has been thoroughly discussed in the literature. However, the underlying different mechanistic pathways of the protein concentration-dependent aggregation of both Au NPs and proteins are poorly understood. The impact of the lipid corona on the protein-induced Au NP aggregation has remained an unresolved issue. In this context, we investigate the interaction of the negatively charged aromatic amino acid (phenylalanine and tyrosine)-functionalized gold nanoparticles (Au-AA NPs) with the positively charged globular protein lysozyme at different protein concentrations and compare the results with those of conventional citrate-functionalized Au NPs (Au-Cit NPs). Next, we conjugate lipids and proteins to Au NPs to impede the aggregation of Au NPs induced by the lysozyme. Our results reveal that the aggregation mechanism of the Au-AA NPs is distinctly different at low and high protein concentrations with the uniqueness of the Au-AA NPs over the Au-Cit NPs. Furthermore, we find that human serum albumin (HSA) protein-conjugated Au-AA and Au-Cit NPs are more effective in preventing the lysozyme-induced Au NP aggregation than bovine serum albumin (BSA)-conjugated Au NPs. For the first time, we also report the significant role of "hard" and "soft" lipid coronas in the aggregation of amino acid (phenylalanine)-functionalized gold nanoparticles in the presence of lysozyme protein.
在蛋白质分子存在的情况下，金纳米颗粒（Au NPs）的聚集及随后的沉淀限制了纳米颗粒在生物医学应用中的效用。到目前为止，文献中已全面讨论了Au NPs的不同性质（尺寸、表面电荷、表面涂层）和蛋白质的不同性质（表面电荷、化学修饰、折叠和未折叠状态）以及溶液的pH值和离子强度对Au NPs和蛋白质聚集的影响。然而，对于Au NPs和蛋白质浓度依赖性聚集的潜在不同机制途径，人们了解甚少。脂质冠对蛋白质诱导的Au NP聚集的影响仍然是一个未解决的问题。在此背景下，我们研究了带负电荷的芳香族氨基酸（苯丙氨酸和酪氨酸）功能化的金纳米颗粒（Au-AA NPs）与带正电荷的球状蛋白溶菌酶在不同蛋白质浓度下的相互作用，并将结果与传统柠檬酸盐功能化的Au NPs（Au-Cit NPs）的结果进行比较。接下来，我们将脂质和蛋白质与Au NPs结合，以阻止溶菌酶诱导的Au NPs聚集。我们的结果表明，Au-AA NPs在低蛋白浓度和高蛋白浓度下的聚集机制明显不同，且Au-AA NPs相对于Au-Cit NPs具有独特性。此外，我们发现人血清白蛋白（HSA）蛋白结合的Au-AA和Au-Cit NPs在防止溶菌酶诱导的Au NP聚集方面比牛血清白蛋白（BSA）结合的Au NPs更有效。我们还首次报道了“硬”脂质冠和“软”脂质冠在溶菌酶蛋白存在下对氨基酸（苯丙氨酸）功能化金纳米颗粒聚集的重要作用。
