Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Departamento de Bioquimica y Biologia Molecular, Facultad de Biologia, and Research Institute Hospital 12 Octubre, Universidad Complutense, José Antonio Novais 2, 28040 Madrid, Spain.
J Control Release. 2015 Dec 28;220(Pt B):642-50. doi: 10.1016/j.jconrel.2015.09.004. Epub 2015 Sep 10.
Many pathologies of the respiratory tract are inadequately treated with existing small molecule-based therapies. The emergence of RNA interference (RNAi) enables the post-transcriptional silencing of key molecular disease factors that cannot readily be targeted with conventional small molecule drugs. Pulmonary administration of RNAi effectors, such as small interfering RNA (siRNA), allows direct delivery into the lung tissue, hence reducing systemic exposure. Unfortunately, the clinical translation of RNAi is severely hampered by inefficient delivery of siRNA therapeutics towards the cytoplasm of the target cells. In order to have a better control of the siRNA delivery process, both extra- and intracellular, siRNAs are typically formulated in nanosized delivery vehicles (nanoparticles, NPs). In the lower airways, which are the targeted sites of action for multiple pulmonary disorders, these siRNA-loaded NPs will encounter the pulmonary surfactant (PS) layer, covering the entire alveolar surface. The interaction between the instilled siRNA-loaded NPs and the PS at this nano-bio interface results in the adsorption of PS components onto the surface of the NPs. The formation of this so-called biomolecular corona conceals the original NP surface and will therefore profoundly determine the biological efficacy of the NP. Though this interplay has initially been regarded as a barrier towards efficient siRNA delivery to the respiratory target cell, recent reports have illustrated that the interaction with PS might also be beneficial for local pulmonary siRNA delivery.
许多呼吸道疾病用现有的基于小分子的疗法治疗效果不佳。RNA 干扰 (RNAi) 的出现使得能够对传统小分子药物难以靶向的关键分子疾病因子进行转录后沉默。RNAi 效应物（如小干扰 RNA (siRNA)）经肺部给药可直接递送至肺组织，从而减少全身暴露。不幸的是，RNAi 的临床转化受到 siRNA 治疗剂向靶细胞细胞质的有效递送至严重阻碍。为了更好地控制 siRNA 的递药过程，无论是细胞外还是细胞内，siRNA 通常被制成纳米级的递药载体（纳米颗粒，NPs）。在气道的下部，这是多种肺部疾病的作用靶点，这些负载 siRNA 的 NPs 将遇到覆盖整个肺泡表面的肺表面活性剂 (PS) 层。在这个纳米生物界面，注入的负载 siRNA 的 NPs 与 PS 之间的相互作用导致 PS 成分吸附到 NPs 的表面上。这种所谓的生物分子冠的形成掩盖了原始 NP 表面，因此将深刻地决定 NP 的生物学功效。尽管这种相互作用最初被认为是有效递送至呼吸道靶细胞的 siRNA 的障碍，但最近的报告表明，与 PS 的相互作用也可能有利于局部肺部 siRNA 的递药。
