Yao Lan, Zhang Geru, Wang Yun, Liu Zhiqiang, Liang Jiale, Sun Jiafei, Li Songhang, Tian Taoran, Lin Yunfeng
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan, 610041, China.
Adv Mater. 2025 Jan;37(4):e2414336. doi: 10.1002/adma.202414336. Epub 2024 Nov 22.
In designing aerosolized drugs, the challenge lies in achieving optimal penetration and retention. Existing delivery systems prioritize larger particles for prolonged intrapulmonary retention, compromising penetration speed. Conversely, smaller nanoparticles face rapid clearance and limited retention. RNA sponges featuring multiple microRNA binding sites exhibit promising potential for gene expression regulation. However, the complex structure of the frequently utilized cyclic RNA sponge impedes rapid penetration and cellular uptake, restricting its application. This study proposes an innovative approach using a compact tetrahedral framework of nucleic acid to construct an inhalable microRNA sponge. Distinguished by its simplified structure, this microRNA sponge ensures effective microRNA inhibition, rapid tissue penetration, and prolonged residency through prompt endocytosis. Validated in acute lung inflammation models, the approach demonstrates swift restoration of local immune homeostasis. This design addresses the critical need for aerosol vehicles that balance efficient penetration and sustained retention, offering a promising solution for effective gene expression regulation.
在设计雾化药物时，挑战在于实现最佳的渗透和滞留效果。现有的递送系统优先考虑较大的颗粒以实现长时间的肺内滞留，但这会影响渗透速度。相反，较小的纳米颗粒面临快速清除和滞留受限的问题。具有多个微小RNA结合位点的RNA海绵在基因表达调控方面展现出了有前景的潜力。然而，常用的环状RNA海绵的复杂结构阻碍了其快速渗透和细胞摄取，限制了其应用。本研究提出了一种创新方法，利用紧凑的四面体核酸框架构建可吸入的微小RNA海绵。这种微小RNA海绵以其简化的结构为特点，通过快速内吞作用确保有效的微小RNA抑制、快速的组织渗透和延长的驻留时间。在急性肺部炎症模型中得到验证，该方法证明了能迅速恢复局部免疫稳态。这种设计满足了对气雾剂载体的关键需求，即在有效渗透和持续滞留之间取得平衡，为有效的基因表达调控提供了一个有前景的解决方案。
