Exploring Maleimide-Based Nanoparticle Surface Engineering to Control Cellular Interactions
Exploring Maleimide-Based Nanoparticle Surface Engineering to Control Cellular Interactions
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DOI：
10.1021/acsanm.9b02541
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发表时间：
2020-03-01
影响因子：
5.9
通讯作者：
Wilhelm, Stefan
中科院分区：
文献类型：
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作者：
Lee, Joanne C.;Donahue, Nathan D.;Wilhelm, Stefan
纳米颗粒细胞相互作用受纳米颗粒表面化学和功能（生物）分子的表面显示控制。为了在纳米粒子表面上缀合和展示含硫醇的（生物）分子，通常利用硫醇和功能性马来酰亚胺基团之间的反应。然而，目前用马来酰亚胺基团修饰纳米颗粒表面的程序很复杂，并且可能导致纳米颗粒聚集。她;我们展示了一种简单、快速（类似于 30 分钟）、高效且稳健的一步式表面工程方案，用于用功能性马来酰亚胺基团修饰金纳米颗粒。我们设计了一种基于异质双功能聚乙二醇的分子，该分子通过其邻吡啶二硫化物（OPSS）末端一步有效地附着在金纳米颗粒表面，使其马来酰亚胺官能团可用于与硫醇的下游反应。利用这种表面工程方法，我们制造了分别具有接近中性和正表面电荷的金纳米粒子。我们证明，通过调整纳米颗粒表面化学性质，可以将组织培养中的模型小鼠乳腺癌 (4T1) 细胞、人乳腺癌 (MDA-MB-231) 细胞和人脐静脉内皮 (HUVEC) 细胞的纳米颗粒细胞摄取效率调整高达 3 个数量级。我们简单高效的基于马来酰亚胺的纳米颗粒表面工程方案创建了一种平台技术，用于将各种含硫醇（生物）分子受控共价表面附着到纳米颗粒上，从而合理设计具有精确细胞相互作用的纳米材料，从而在生物分析和纳米医学中广泛应用。
Nanoparticle cellular interactions are governed by nanoparticle surface chemistry and the surface display of functional (bio)molecules. To conjugate and display thiol-containing (bio)molecules on nanoparticle surfaces, reactions between thiols and functional maleimide groups are often exploited. However, current procedures for modifying nanoparticle surfaces with maleimide groups are complex and can result in nanoparticle aggregation. Her; we demonstrate a straightforward, fast (similar to 30 min), efficient, and robust one-step surface engineering protocol for modifying gold nanoparticles with functional maleimide groups. We designed a hetero-bifunctional poly(ethylene glycol)-based molecule that attaches efficiently to the gold nanoparticle surface in a single step via its orthopyridyl disulfide (OPSS) terminal end, leaving its maleimide functional group available for downstream reaction with thiols. Using this surface engineering approach, we fabricated gold nanoparticles with near neutral and positive surface charges, respectively. We demonstrate that nanoparticle cellular uptake efficiencies in model mouse breast cancer (4T1) cells, human breast cancer (MDA-MB-231) cells, and human umbilical vein endothelial (HUVEC) cells in tissue culture can be tuned by up to 3 orders of magnitude by adjusting nanoparticle surface chemistry. Our straightforward and efficient maleimide-based nanoparticle surface engineering protocol creates a platform technology for controlled covalent surface attachment of a variety of thiol-containing (bio)molecules to nanoparticles for rational design of nanomaterials with precise cellular interactions for widespread applications in bioanalysis and nanomedicine.