School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, Singapore.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, Singapore; Neuroscience@ NTU, Interdisciplinary Graduate Programme, Nanyang Technological University, Singapore.
Biomaterials. 2023 Nov;302:122325. doi: 10.1016/j.biomaterials.2023.122325. Epub 2023 Sep 15.
A major bottleneck in drug/gene delivery to enhance tissue regeneration after injuries is to achieve targeted delivery to the cells of interest. Unfortunately, we have not been able to attain effective targeted drug delivery in tissues due to the lack of efficient delivery platforms. Since specific cell-cell interactions exist to impart the unique structure and functionality of tissues and organs, we hypothesize that such specific cellular interactions may also be harnessed for drug delivery applications in the form of cell membrane coatings. Here, we employed neural cell-derived membrane coating technique on DNA nanogels to improve target specificity. The efficacy of neural cell membrane-coated DNA nanogels (NCM-nanogels) was demonstrated by using four types of cell membranes derived from the central nervous system (CNS), namely, astrocytes, microglia, cortical neurons, and oligodendrocyte progenitor cells (OPCs). A successful coating of NCMs over DNA nanogels was confirmed by dynamic light scattering, zeta potential measurements and transmission electron microscopy. Subsequently, an overall improvement in cellular uptake of NCM-nanogels over uncoated DNA nanogels (p < 0.005) was seen. Additionally, we observed a selective uptake of OPC membrane-coated DNA nanogels (NCM-O mem) by oligodendrocytes over other cell types both in vitro and in vivo. Our quantitative polymerase chain reaction (qPCR) results also showed selective and effective gene knockdown capacity of NCM-O mem for OPC transfection. The findings in this work may be beneficial for future drug delivery applications targeted at the CNS.
在损伤后增强组织再生的药物/基因传递中，一个主要的瓶颈是实现对靶细胞的靶向传递。不幸的是，由于缺乏有效的传递平台，我们还不能在组织中实现有效的靶向药物传递。由于特定的细胞-细胞相互作用赋予了组织和器官的独特结构和功能，我们假设这种特定的细胞相互作用也可以通过细胞膜涂层的形式被用于药物传递应用。在这里，我们采用神经细胞衍生的细胞膜涂层技术在 DNA 纳米凝胶上，以提高靶向特异性。通过使用源自中枢神经系统（CNS）的四种细胞膜（星形胶质细胞、小胶质细胞、皮质神经元和少突胶质细胞祖细胞（OPC）），证明了神经细胞膜涂层 DNA 纳米凝胶（NCM-纳米凝胶）的功效。通过动态光散射、ζ电位测量和透射电子显微镜证实了 NCM 成功地涂层在 DNA 纳米凝胶上。随后，观察到 NCM-纳米凝胶的细胞摄取总体上优于未涂层的 DNA 纳米凝胶（p<0.005）。此外，我们观察到 OPC 膜涂层 DNA 纳米凝胶（NCM-O mem）在体外和体内均被少突胶质细胞选择性摄取，而其他细胞类型则没有。我们的定量聚合酶链反应（qPCR）结果还表明，NCM-O mem 对 OPC 转染具有选择性和有效的基因敲低能力。这项工作的发现可能对未来针对中枢神经系统的药物传递应用有益。
