Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
School of Veterinary Medicine, University College Dublin (UCD), Dublin 4, Ireland.
Small. 2019 Aug;15(33):e1901679. doi: 10.1002/smll.201901679. Epub 2019 Jul 3.
Nanoparticle-based drug delivery systems have attracted significant interest owing to their promise as tunable platforms that offer improved intracellular release of cargo therapeutics. However, significant challenges remain in maintaining the physiological stability of the mucosal matrix due to the nanoparticle-induced reduction in the matrix diffusivity and promotion of mucin aggregation. Such aggregation also adversely impacts the permeability of the nanoparticles, and thus, diminishes the efficacy of nanoparticle-based formulations. Here, an entirely complementary approach is proposed to the existing nanoparticle functionalization methods to address these challenges by using trehalose, a naturally occurring disaccharide that offers exceptional protein stabilization. Plasmon-enhanced Raman spectroscopy and far-red fluorescence emission of the plasmonic silver nanoparticulate clusters are harnessed to create a unique dual-functional, aggregating, and imaging agent that obviates the need of an additional reporter to investigate mucus-nanoparticle interactions. These spectroscopy-based density mapping tools uncover the mechanism of mucus-nanoparticle interactions and establish the protective role of trehalose microenvironment in minimizing the nanoparticle aggregation. Thus, in contrast to the prevailing belief, these results demonstrate that nonfunctionalized nanoparticles may rapidly penetrate through mucus barriers, and by leveraging the bioprotectant attributes of trehalose, an in vivo milieu for efficient mucosal drug delivery can be generated.
基于纳米粒子的药物输送系统因其作为可调平台的潜力而引起了极大的关注，该平台可提供货物治疗剂的细胞内释放改善。然而，由于纳米粒子诱导的基质扩散率降低和粘蛋白聚集的促进，维持粘膜基质的生理稳定性仍然存在重大挑战。这种聚集还会对纳米粒子的渗透性产生不利影响，从而降低基于纳米粒子的制剂的功效。在这里，提出了一种与现有纳米粒子功能化方法完全互补的方法，通过使用海藻糖来解决这些挑战，海藻糖是一种天然存在的二糖，具有出色的蛋白质稳定性。利用等离子体增强的喇曼光谱和等离子体银纳米颗粒簇的远红荧光发射来创建独特的双功能、聚集和成像剂，无需额外的示踪剂来研究粘液-纳米粒子相互作用。这些基于光谱的密度映射工具揭示了粘液-纳米粒子相互作用的机制，并确立了海藻糖微环境在最小化纳米粒子聚集方面的保护作用。因此，与普遍的观点相反，这些结果表明，未功能化的纳米粒子可能会迅速穿透粘液屏障，并且通过利用海藻糖的生物保护特性，可以产生用于有效粘膜药物输送的体内环境。
