NUS Graduate School of Integrative Sciences and Engineering , National University of Singapore , 117456 Singapore.
Department of Biomedical Engineering , National University of Singapore , 117583 Singapore.
ACS Appl Mater Interfaces. 2019 Feb 6;11(5):4777-4789. doi: 10.1021/acsami.8b18107. Epub 2019 Jan 29.
Mucus is an endogenous viscoelastic biopolymer barrier that limits the entry of foreign pathogens and therapeutic carriers to the underlying mucosal cells. This could be overcome with a hydrophilic and nonpositively charged carrier surface that minimizes interactions with the mucin glycoprotein fibers. Although PEGylation remains an attractive surface strategy to enhance mucopenetration, cell uptake of PEGylated nanoparticles (NPs) often remains poor. Here, we demonstrated polydopamine (PDA) coating to enhance both mucopenetration and cell uptake of NPs. PDA was polymerized on carboxylated polystyrene (PS) NPs to form a PDA coating, and the resulting PS-PDA achieved a similar level of mucopenetration as our PEGylated PS (PS-PEG) positive control in three separate studies: NP-mucin interaction test, transwell assay, and multiple particle tracking. Compared to water, the diffusions of PS-PDA and PS-PEG in reconstituted mucus solution were only 3.5 and 2.4 times slower, respectively, whereas the diffusion of bare PS was slowed by up to 250 times. However, the uptake of PS-PDA (61.2 ± 6.1%) was almost three times higher than PS-PEG (24.6 ± 5.4%) in T24 cells, which were used as a model for underlying mucosal cells. Our results showed a novel unreported functionality of PDA coating in enhancing both mucopenetration and cell uptake of NPs for mucosal drug delivery applications, not possible with conventional PEGylation strategies.
黏液是一种内源性的黏弹生物聚合物屏障，它限制了外来病原体和治疗载体进入底层黏膜细胞。通过使用亲水性和不带正电荷的载体表面，可以克服这一问题，使载体表面与黏蛋白糖蛋白纤维的相互作用最小化。尽管聚乙二醇（PEG）化仍然是一种增强黏膜穿透性的有吸引力的表面策略，但 PEG 化纳米颗粒（NPs）的细胞摄取率通常仍然较低。在这里，我们证明了聚多巴胺（PDA）涂层可以增强 NPs 的黏膜穿透性和细胞摄取率。在羧基化聚苯乙烯（PS） NPs 上聚合 PDA 形成 PDA 涂层，所得 PS-PDA 在三项独立研究中实现了与我们的 PEG 化 PS（PS-PEG）阳性对照相似的黏膜穿透性：NP-黏液相互作用测试、Transwell 测定和多颗粒跟踪。与水相比，PS-PDA 和 PS-PEG 在重建的黏液溶液中的扩散速度分别仅慢 3.5 倍和 2.4 倍，而裸 PS 的扩散速度则被减缓了多达 250 倍。然而，PS-PDA（61.2±6.1%）在 T24 细胞中的摄取率几乎是 PS-PEG（24.6±5.4%）的三倍，T24 细胞被用作底层黏膜细胞的模型。我们的结果表明，PDA 涂层具有一种新的、未被报道的功能，可增强 NPs 的黏膜穿透性和细胞摄取率，这是传统 PEG 化策略所不可能实现的。
