Biological Engineering Discipline, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
Center for Biomedical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
ACS Appl Bio Mater. 2021 Apr 19;4(4):3350-3359. doi: 10.1021/acsabm.0c01668. Epub 2021 Mar 10.
Multiple endocytic pathways operate on the plasma membrane of cells at any moment with diverse but specific cellular functions. Knowledge of uptake of synthetic nanoparticles and ligands with respect to endocytic pathways is crucial to device the appropriate ligands for therapeutic delivery into differentiated neurons for targeting neuronal diseases. We herein explore the mechanisms of cellular uptake of 3D tetrahedral DNA nanocages at different stages of differentiating neurons. We monitored the uptake, kinetics, and dynamics of DNA cages of different geometries, and interestingly we find a specific pattern and adaptability of the uptake of DNA devices with respect to the geometry of the ligand and specific endocytic pathways. We find that tetrahedral DNA nanocages get endocytosed mostly via clathrin-mediated endocytosis in fully mature neurons. This endocytic uptake and intracellular choreography of DNA nanodevices will help us design the smartly targeted biotherapeutics for targeting neuronal disorders.
多种内吞途径在细胞的质膜上随时运作,具有不同但特定的细胞功能。了解合成纳米颗粒和配体相对于内吞途径的摄取对于为靶向神经元疾病的治疗性递送入分化神经元设计适当的配体至关重要。本文探索了在分化神经元的不同阶段,3D 四面体形 DNA 纳米笼的细胞摄取机制。我们监测了不同几何形状的 DNA 笼的摄取、动力学和动力学,有趣的是,我们发现 DNA 器件的摄取具有特定的模式和适应性,与配体的几何形状和特定的内吞途径有关。我们发现四面体 DNA 纳米笼主要通过网格蛋白介导的内吞作用在完全成熟的神经元中被内吞。这种 DNA 纳米器件的内吞摄取和细胞内编排将帮助我们设计针对神经元疾病的智能靶向生物疗法。