School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
ACS Appl Mater Interfaces. 2021 Dec 1;13(47):55840-55850. doi: 10.1021/acsami.1c16543. Epub 2021 Nov 18.
Targeted drug delivery to specific neural cells within the central nervous system (CNS) plays important roles in treating neurological disorders, such as neurodegenerative (e.g., targeting neurons) and demyelinating diseases [e.g., targeting oligodendrocytes (OLs)]. However, the presence of many other cell types within the CNS, such as microglial and astrocytes, may lead to nonspecific uptake and subsequent side effects. As such, exploring an effective and targeted drug delivery system is of great necessity. Synthetic micro-/nanoparticles that have been coated with biologically derived cellular membranes have emerged as a new class of drug delivery vehicles. However, the use of neural cell-derived membrane coatings remains unexplored. Here, we utilized this technique and demonstrated the efficacy of targeted delivery by using four types of cell membranes that were derived from the CNS, namely, microglial, astrocytes, oligodendrocyte progenitor cells (OPCs), and cortical neurons. A successful cell membrane coating over poly(ε-caprolactone) nanoparticles (NPs) was confirmed using dynamic light scattering, zeta potential measurements, and transmission electron microscopy. Subsequently, an extensive screening of these cell membrane-coated NPs was carried out on various CNS cells. Results suggested that microglial and OLs were the most sensitive cell types toward cell membrane-coated NPs. Specifically, cell membrane-coated NPs significantly enhanced the uptake efficiency of OLs ( < 0.001). Additionally, a temporal uptake study indicated that the OLs took up microglial membrane-coated NPs (DPP-PCL-M Mem) most efficiently. Besides that, coating the NPs with four types of the CNS cell membrane did not result in obvious specific uptake in microglial but reduced the activation of microglial, especially for DPP-PCL-M Mem ( < 0.01). Taken together, DPP-PCL-M Mem were uptaken most efficiently in OLs and did not induce significant microglial activation and may be most suitable for CNS drug delivery applications.
靶向递送至中枢神经系统（CNS）内的特定神经细胞在治疗神经退行性疾病（如靶向神经元）和脱髓鞘疾病（如靶向少突胶质细胞[OLs]）等方面发挥着重要作用。然而，CNS 中存在许多其他细胞类型，如小胶质细胞和星形胶质细胞，这可能导致非特异性摄取和随后的副作用。因此，探索有效的靶向药物递送系统非常必要。用生物衍生的细胞膜包被的合成微/纳米颗粒已成为一类新的药物递送载体。然而，神经细胞衍生的细胞膜涂层的使用仍有待探索。在这里，我们利用该技术，通过使用源自 CNS 的四种细胞膜（小胶质细胞、星形胶质细胞、少突胶质细胞前体细胞[OPC]和皮质神经元），展示了靶向递药的功效。通过动态光散射、Zeta 电位测量和透射电子显微镜证实了聚（ε-己内酯）纳米颗粒（NPs）上成功的细胞膜包被。随后，对这些细胞膜包被的 NPs 进行了广泛的 CNS 细胞筛选。结果表明，小胶质细胞和 OLs 是对细胞膜包被的 NPs 最敏感的细胞类型。具体来说，细胞膜包被的 NPs 显著提高了 OLs 的摄取效率（<0.001）。此外，时间摄取研究表明，OLs 最有效地摄取小胶质细胞膜包被的 NPs（DPP-PCL-M Mem）。除此之外，用四种 CNS 细胞膜包被 NPs 不会导致小胶质细胞中明显的特异性摄取，但会降低小胶质细胞的激活，特别是对于 DPP-PCL-M Mem（<0.01）。总之，DPP-PCL-M Mem 最有效地被 OLs 摄取，并且不会引起明显的小胶质细胞激活，可能最适合 CNS 药物递送应用。
