Patterning of Self-Assembled Monolayers of Amphiphilic Multisegment Ligands on Nanoparticles and Design Parameters for Protein Interactions
Patterning of Self-Assembled Monolayers of Amphiphilic Multisegment Ligands on Nanoparticles and Design Parameters for Protein Interactions
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DOI：
10.1021/acsnano.1c08695
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发表时间：
2022-05-22
期刊：
影响因子：
17.1
通讯作者：
Heinz，Hendrik
中科院分区：
文献类型：
--
作者：
Hoff，Samuel E.;Di Silvio，Desire;Heinz，Hendrik
具有特定配体的纳米粒子的功能化有助于控制特定的诊断和治疗反应，如蛋白质吸附、细胞靶向和循环。精确的传递关键取决于对表面化学、配基动力学以及与生化环境的相互作用的基本了解。由于从实验上对纳米颗粒结合配体的结构和动力学的原子尺度的了解有限，嫁接密度和配体化学与可观察的性质(如亲水性和蛋白质相互作用)的关系在很大程度上仍不清楚。在这项工作中，我们揭示了由多段配体组成的自组装单分子膜(SAM)是如何在金纳米颗粒上模拟混合疏水和亲水配体涂层的，包括对图案、亲水性和特定识别性能的控制。我们的结果是用皮米分辨率的CHARMM36界面力场的分子动力学模拟得到的，并与实验进行了比较。配体疏水性的微小变化，通过调整N端烷基团的长度，以倍数调节水的渗透性，并控制烷基链的表面有序性从0到70%的规律性。进一步的参数包括配体的接枝密度、纳米颗粒表面的曲率、溶剂的类型和总的配体长度，这些都得到了详细的考察。我们解释了多链段配基自组装膜形成异相模式的热力学根源，并说明了纳米颗粒表面不同程度的配基有序性如何影响与牛血清白蛋白的相互作用。由此产生的设计原则可应用于各种配基化学，以定制功能化纳米颗粒在生物介质中的行为，并提高治疗效率。
Functionalization of nanoparticles with specific ligands is helpful to control specific diagnostic and therapeutic responses such as protein adsorption, cell targeting, and circulation. Precision delivery critically depends on a fundamental understanding of the interplay between surface chemistry, ligand dynamics, and interaction with the biochemical environment. Due to limited atomic-scale insights into the structure and dynamics of nanoparticle-bound ligands from experiments, relationships of grafting density and ligand chemistry to observable properties such as hydrophilicity and protein interactions remain largely unknown. In this work, we uncover how self-assembled monolayers (SAMs) composed of multisegment ligands such as thioalkyl-PEG-(N-alkyl)amides on gold nanoparticles can mimic mixed hydrophobic and hydrophilic ligand coatings, including control of patterns, hydrophilicity, and specific recognition properties. Our results are derived from molecular dynamics simulations with the INTERFACE-CHARMM36 force field at picometer resolution and comparisons to experiments. Small changes in ligand hydrophobicity, via adjusting the length of the N-terminal alkyl groups, tune water penetration by multiples and control superficial ordering of alkyl chains from 0 to 70% regularity. Further parameters include the grafting density of the ligands, curvature of the nanoparticle surfaces, type of solvent, and overall ligand length, which were examined in detail. We explain the thermodynamic origin of the formation of heterogeneous patterns of multisegment ligand SAMs and illustrate how different degrees of ligand order on the nanoparticle surface affect interactions with bovine serum albumin. The resulting design principles can be applied to a variety of ligand chemistries to customize the behavior of functionalized nanoparticles in biological media and enhance therapeutic efficiency.