Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, Departamento de Fisicoquímica, CONICET, INFIQC, Ciudad Universitaria, X5000HUA, Córdoba, Argentina.
Departamento de Química Biológica Ranwel Caputto, CONICET, CIQUIBIC, Ciudad Universitaria, X5000HUA, Córdoba, Argentina.
Colloids Surf B Biointerfaces. 2020 Jul;191:110998. doi: 10.1016/j.colsurfb.2020.110998. Epub 2020 Mar 27.
Layered double hydroxide nanoparticles (LDH-NPs) constitute promising nanocarriers for drug and gene delivery. Although their cell internalization has been studied, the interaction between LDH-NPs and biological membrane models, such as giant unilamellar vesicles (GUVs), remains unexplored. These vesicles are widely-used membrane models that allow minimizing the complexity and uncertainty associated with biological systems to study the physical interactions in the absence of cell metabolism effects. With such an approach the physicochemical properties of the membrane can be differentiated from the biological functionalities involved in cell internalization and the membrane-mediated internalization can be directly understood. In this work, we describe for the first time the interaction of LDH-NPs with freestanding negatively charged POPC:POPS GUVs by fluorescence microscopy. The experiments were performed with fluorescein labeled LDH-NPs of about 100 nm together with different fluorophores in order to evaluate the NPs interactions with the vesicles as well as their impact on the membrane morphology and permeability. Positively charged LDH-NPs are electrostatically accumulated at the GUVs membrane, altering its lateral phospholipid distribution and increasing the stiffness and permeability of the membrane. The adsorption of albumin (LDH@ALB) or polyacrylic acid (LDH@PA) passivates the surface of LDH-NPs eliminating long-range electrostatic attraction. The absence of membrane-mediated internalization of either LDH@ALB or LDH@PA, represents an advantage in the use of LDH-NPs as drug or nucleic acids nanocarriers, because suitable functionalization will allow an optimal cell targeting.
层状双氢氧化物纳米颗粒（LDH-NPs）是一种很有前途的药物和基因传递的纳米载体。虽然已经研究了它们的细胞内化，但 LDH-NPs 与生物膜模型（如巨大的单分子层囊泡（GUVs））之间的相互作用仍然未知。这些囊泡是广泛使用的膜模型，它们可以最小化与生物系统相关的复杂性和不确定性，以在没有细胞代谢效应的情况下研究物理相互作用。通过这种方法，可以将膜的物理化学性质与参与细胞内化的生物学功能区分开来，并可以直接理解膜介导的内化。在这项工作中，我们首次通过荧光显微镜描述了 LDH-NPs 与游离的带负电荷的 POPC:POPS GUVs 的相互作用。实验是用约 100nm 的荧光素标记的 LDH-NPs 与不同的荧光团一起进行的，以评估 NPs 与囊泡的相互作用及其对膜形态和通透性的影响。带正电荷的 LDH-NPs 静电积累在 GUVs 膜上，改变其侧向磷脂分布，增加膜的刚性和通透性。白蛋白（LDH@ALB）或聚丙烯酸（LDH@PA）的吸附使 LDH-NPs 的表面钝化，消除了长程静电吸引。LDH@ALB 或 LDH@PA 都没有发生膜介导的内化，这在将 LDH-NPs 用作药物或核酸纳米载体时是一个优势，因为适当的功能化将允许进行最佳的细胞靶向。
