Park Joonyoung, Brust Tarsis F, Lee Hong Jae, Lee Sang Cheon, Watts Val J, Yeo Yoon
Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
ACS Nano. 2014 Apr 22;8(4):3347-56. doi: 10.1021/nn405809c. Epub 2014 Mar 19.
The surface of a polymeric nanoparticle (NP) is often functionalized with cell-interactive ligands and/or additional polymeric layers to control NP interaction with cells and proteins. However, such modification is not always straightforward when the surface is not chemically reactive. For this reason, most NP functionalization processes employ reactive linkers or coupling agents or involve prefunctionalization of the polymer, which are complicated and inefficient. Moreover, prefunctionalized polymers can lose the ability to encapsulate and retain a drug if the added ligands change the chemical properties of the polymer. To overcome this challenge, we use dopamine polymerization as a way of functionalizing NP surfaces. This method includes brief incubation of the preformed NPs in a weak alkaline solution of dopamine, followed by secondary incubation with desired ligands. Using this method, we have functionalized poly(lactic-co-glycolic acid) (PLGA) NPs with three representative surface modifiers: a small molecule (folate), a peptide (Arg-Gly-Asp), and a polymer [poly(carboxybetaine methacrylate)]. We confirmed that the modified NPs showed the expected cellular interactions with no cytotoxicity or residual bioactivity of dopamine. The dopamine polymerization method is a simple and versatile surface modification method, applicable to a variety of NP drug carriers irrespective of their chemical reactivity and the types of ligands.
聚合物纳米颗粒（NP）的表面通常用细胞相互作用配体和/或额外的聚合物层进行功能化，以控制NP与细胞和蛋白质的相互作用。然而，当表面没有化学反应活性时，这种修饰并不总是那么直接。因此，大多数NP功能化过程采用反应性连接剂或偶联剂，或者涉及聚合物的预功能化，这些方法既复杂又低效。此外，如果添加的配体改变了聚合物的化学性质，预功能化的聚合物可能会失去包封和保留药物的能力。为了克服这一挑战，我们使用多巴胺聚合作为功能化NP表面的一种方法。该方法包括将预先形成的NP在多巴胺的弱碱性溶液中短暂孵育，然后与所需配体进行二次孵育。使用这种方法，我们用三种代表性的表面修饰剂对聚乳酸-乙醇酸共聚物（PLGA）NP进行了功能化：一种小分子（叶酸）、一种肽（精氨酸-甘氨酸-天冬氨酸）和一种聚合物[聚（甲基丙烯酸羧酸甜菜碱）]。我们证实，修饰后的NP表现出预期的细胞相互作用，且没有多巴胺的细胞毒性或残留生物活性。多巴胺聚合方法是一种简单且通用的表面修饰方法，适用于各种NP药物载体，无论其化学反应活性和配体类型如何。
