Human Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
ACS Nano. 2021 Oct 26;15(10):15803-15814. doi: 10.1021/acsnano.1c03151. Epub 2021 Sep 29.
The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated. This microvillus-mediated adhesion (MMA) has been observed using ceria and magnetite NPs with a dimension of <40 nm functionalized with polyacrylic acid but not using NPs with a neutral or positive functionalization. Such an adhesion was not cell specific, as it was demonstrated in three different cell lines. MMA was also reduced by modifications of the microvillus lipid rafts, obtained by depleting cholesterol and altering synthesis of sphingolipids. We found a direct relationship between MAA, cell cycle, and density of microvilli. The evidence suggests that MMA differs from the commonly described uptake mechanisms and might represent an interesting alternative approach for selective NP delivery.
纳米颗粒（NPs）的细胞摄取是纳米医学的关键步骤，也是理解纳米材料与生物系统相互作用的关键点。到目前为止，还没有确定特定的摄取机制，因为这些 NPs 通常通过少数几种已知的胞吞作用机制之一被细胞内化。本文证明了一种由微绒毛黏附介导的替代内化途径。这种微绒毛介导的黏附（MMA）是使用<40nm 的功能化聚丙烯酸的氧化铈和磁铁矿 NPs 观察到的，但不能使用中性或正功能化的 NPs。这种黏附不是细胞特异性的，因为在三种不同的细胞系中都得到了证明。通过耗尽胆固醇和改变鞘脂合成来修饰微绒毛脂筏，也可以减少 MMA。我们发现 MMA 与细胞周期和微绒毛密度之间存在直接关系。这些证据表明，MMA 与通常描述的摄取机制不同，可能代表一种用于选择性 NP 递送的有趣替代方法。
