Langmuir. 2019 Aug 13;35(32):10631-10639. doi: 10.1021/acs.langmuir.9b01395. Epub 2019 Jul 25.
Membrane wrapping pathway of injectable hydrogels (IHs) plays a vital role in the nanocarrier effectiveness and biomedical safety. Although considerable progress in understanding this complicated process has been made, the mechanism behind this process has remained elusive. Herein, with the help of large-scale dissipative particle dynamics simulations, we explore the molecular mechanism of membrane wrapping by systematically examining the IH architectures and hydrogel-lipid binding strengths. To the best of our knowledge, this is the first report on the membrane wrapping pathway on which IHs transform from vertical capillary adhesion to lateral compressed wrapping. This transformation results from the elastocapillary deformation of networked gels and nanoscale confinement of the bilayer membrane, and it takes long time for the IHs to be fully wrapped owing to the high energy barriers and wrapping-induced shape deformation. Collapsed morphologies and small compressed angles are identified in the IH capsules with a thick shell or strong binding strength to lipids. In addition, the IHs binding intensively to the membrane exhibit special nanoscale mixing and favorable deformability during the wrapping process. Our study provides a detailed mechanistic understanding of the influence of architecture and binding strength on the IH membrane wrapping efficiency. This work may serve as rational guidance for the design and fabrication of IH-based drug carriers and tissue engineering.
可注射水凝胶（IHs）的膜包裹途径在纳米载体的有效性和生物医学安全性方面起着至关重要的作用。尽管在理解这一复杂过程方面已经取得了相当大的进展，但这一过程的机制仍然难以捉摸。在此，我们借助大规模耗散粒子动力学模拟，通过系统地研究 IH 结构和水凝胶-脂质结合强度，探索膜包裹的分子机制。据我们所知，这是第一篇关于 IH 从垂直毛细粘附到横向压缩包裹的膜包裹途径的报告。这种转变源于网络凝胶的弹毛细管变形和双层膜的纳米尺度限制，由于高能量障碍和包裹诱导的形状变形，IH 完全包裹需要很长时间。在具有厚壳或与脂质强结合力的 IH 胶囊中，会出现坍塌形态和小的压缩角度。此外，在包裹过程中，与膜强烈结合的 IH 表现出特殊的纳米尺度混合和良好的变形能力。我们的研究为结构和结合强度对 IH 膜包裹效率的影响提供了详细的机制理解。这项工作可以为基于 IHs 的药物载体和组织工程的设计和制造提供合理的指导。
