State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024, Dalian, China.
School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024, Dalian, China.
ACS Nano. 2023 Feb 14;17(3):2813-2828. doi: 10.1021/acsnano.2c11147. Epub 2023 Jan 31.
The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle-mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle-mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.
纳米颗粒在黏液中的穿透行为取决于纳米颗粒的物理化学性质和黏液微环境，这是由于颗粒-黏蛋白相互作用和黏蛋白网格空间过滤效应的存在。迄今为止，仍不清楚纳米颗粒的表面性质如何影响它们在各种生理和病理生理条件下的黏液穿透行为。在这项研究中，我们制备了具有受控表面配体密度的胺基、羧基和聚乙二醇（PEG）修饰的二氧化硅纳米颗粒（SNP）的综合文库。通过使用多种粒子跟踪技术，我们研究了这些 SNP 穿透黏液的机制。结果发现，在等密度条件下，PEG 和胺修饰的 SNP 表现出 pH 不依赖性固定，而羧基修饰的 SNP 仅在弱碱性黏液中表现出增强的运动。生物物理特性表明，由于静电相互作用和氢键与黏蛋白的相互作用，胺基和羧基修饰的 SNP 被捕获在黏液中。相比之下，高密度 PEG 化表面形成了一种刷状构象，屏蔽了颗粒-黏蛋白的相互作用。我们进一步使用小鼠气道分布模型研究了表面性质依赖性的黏液穿透行为。这项研究为设计用于预防和治疗肺部疾病的高效跨黏液纳米载体提供了见解。
