Song Yo Han, De Ranjit, Lee Kang Taek
Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Cheongam-Ro 77, Pohang, Gyeongbuk 37673, Korea.
Pharmaceutics. 2021 Jan 14;13(1):102. doi: 10.3390/pharmaceutics13010102.
Tauopathy is the aggregation phenomenon of tau proteins and associated with neurodegenerative diseases. It metastasizes via the transfer of tau aggregates to adjacent neuron cells; however, the mechanism has not yet been fully understood. Moreover, if the materials used for designing drug delivery system to treat such neurodegenerative diseases do not undergo biodegradation or exocytosis but remains in cells or tissues, they raise concerns about their possible negative impacts. In this study, the uptake and delivery mechanisms of nano-sized carriers in tau aggregated neuron cells were investigated employing polyelectrolyte-functionalized upconversion nanoparticles (UCNPs) of diameter ~100 nm. Investigation through bioimaging was carried out by irradiating the particles with near-infrared light. Here, forskolin and okadaic acid were employed to induce tau aggregation into healthy neuron cells. It was noticed that the tau-aggregated neuron cells, when treated with relatively large sized UCNPs, showed uptake efficiency similar to that of normal neuron cells however their intracellular transport and exocytosis were impacted, and most of the carriers remained accumulated around lysosome. This demonstrates that metastasis mechanisms of tauopathy can get influenced by the size of carriers and are to be considered during their pharmacokinetic studies which is often not addressed in many drug delivery studies.
tau蛋白病是tau蛋白的聚集现象，与神经退行性疾病相关。它通过tau聚集体转移到相邻神经元细胞而发生转移；然而，其机制尚未完全清楚。此外，如果用于设计治疗此类神经退行性疾病的药物递送系统的材料不发生生物降解或胞吐作用，而是留在细胞或组织中，人们会担心它们可能产生的负面影响。在本研究中，使用直径约100 nm的聚电解质功能化上转换纳米颗粒（UCNP）研究了纳米级载体在tau聚集神经元细胞中的摄取和递送机制。通过用近红外光照射颗粒进行生物成像研究。在此，使用福斯可林和冈田酸诱导tau在健康神经元细胞中聚集。值得注意的是，用相对较大尺寸的UCNP处理时，tau聚集的神经元细胞显示出与正常神经元细胞相似的摄取效率，但其细胞内转运和胞吐作用受到影响，并且大多数载体仍积聚在溶酶体周围。这表明tau蛋白病的转移机制可能会受到载体大小的影响，并且在其药代动力学研究中应予以考虑，而这在许多药物递送研究中往往未得到解决。
