Mucosal tissues constitute the largest interface between the body and the surrounding environment and they regulate the access of molecules, supramolecular structures, particulate matter, and pathogens into it. All mucosae are characterized by an outer mucus layer that protects the underlying cells from physicochemical, biological and mechanical insults, a mono-layered or stratified epithelium that forms tight junctions and controls the selective transport of solutes across it and associated lymphoid tissues that play a sentinel role. Mucus is a gel-like material comprised mainly of the glycoprotein mucin and water and it displays both hydrophilic and hydrophobic domains, a net negative charge, and high porosity and pore interconnectivity, providing an efficient barrier for the absorption of therapeutic agents. To prolong the residence time, absorption and bioavailability of a broad spectrum of active compounds upon mucosal administration, mucus-penetrating and mucoadhesive particles have been designed by tuning the chemical composition, the size, the density, and the surface properties. The benefits of utilizing nanomaterials that interact intimately with mucosae by different mechanisms in the nanomedicine field have been extensively reported. To ensure the safety of these nanosystems, their compatibility is evaluated in vitro and in vivo in preclinical and clinical trials. Conversely, there is a growing concern about the toxicity of nanomaterials dispersed in air and water effluents that unintentionally come into contact with the airways and the gastrointestinal tract. Thus, deep understanding of the key nanomaterial properties that govern the interplay with mucus and tissues is crucial for the rational design of more efficient drug delivery nanosystems (nanomedicine) and to anticipate the fate and side-effects of nanoparticulate matter upon acute or chronic exposure (nanotoxicology). This review initially overviews the complex structural features of mucosal tissues, including the structure of mucus, the epithelial barrier, the mucosal-associated lymphatic tissues and microbiota. Then, the most relevant investigations attempting to identify and validate the key particle features that govern nanomaterial–mucosa interactions and that are relevant in both nanomedicine and nanotoxicology are discussed in a holistic manner. Finally, the most popular experimental techniques and the incipient use of mathematical and computational models to characterize these interactions are described.

中文翻译：

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控制纳米材料与粘膜相互作用的分子和细胞线索：从纳米医学到纳米毒理学。

粘膜组织构成了人体与周围环境之间最大的界面，它们调节分子，超分子结构，颗粒物和病原体的进入。所有粘膜的特征是外层粘液层可保护基础细胞免受物理化学，生物和机械损伤，单层或分层的上皮形成紧密的连接并控制溶质在其上的选择性转运以及与前哨有关的淋巴组织角色。粘液是主要由糖蛋白粘蛋白和水组成的凝胶状材料，它既显示亲水域又显示疏水域，具有负净电荷，并且具有高孔隙率和孔互连性，为吸收治疗剂提供了有效的屏障。为了延长停留时间，通过调节化学成分，大小，密度和表面性质，设计了粘膜给药后广泛的活性化合物的吸收和生物利用度，粘液渗透性和粘膜粘附性颗粒。已经广泛报道了利用通过纳米医学领域中的不同机制与粘膜紧密相互作用的纳米材料的益处。为了确保这些纳米系统的安全性，评估了它们的兼容性 已经广泛报道了利用通过纳米医学领域中的不同机制与粘膜紧密相互作用的纳米材料的益处。为了确保这些纳米系统的安全性，评估了它们的兼容性 已经广泛报道了利用通过纳米医学领域中的不同机制与粘膜紧密相互作用的纳米材料的益处。为了确保这些纳米系统的安全性，评估了它们的兼容性体外和体内在临床前和临床试验中。相反，人们越来越关注分散在空气和废水中的纳米材料的毒性，这些材料无意中与呼吸道和胃肠道接触。因此，深入了解控制与粘液和组织相互作用的关键纳米材料特性对于合理设计更高效的药物输送纳米系统（纳米医学）以及预测纳米颗粒物质在急性或慢性暴露下的命运和副作用至关重要（纳米毒理学）。本文首先概述了粘膜组织的复杂结构特征，包括粘液的结构，上皮屏障，与粘膜相关的淋巴组织和微生物群。然后，整体讨论了试图鉴定和验证控制纳米材料与粘膜相互作用以及与纳米药物和纳米毒理学相关的关键颗粒特征的最相关研究。最后，描述了最流行的实验技术以及数学和计算模型的初期使用来表征这些相互作用。