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超顺磁性氧化铁纳米颗粒在磁场中可引导螺旋神经节神经元的突起生长和方向。

Neurite Extension and Orientation of Spiral Ganglion Neurons Can Be Directed by Superparamagnetic Iron Oxide Nanoparticles in a Magnetic Field.

机构信息

State Key Laboratory of Bioelectronics, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, People's Republic of China.

School of Biology, Food and Environment, Hefei University, Hefei, 230601, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Jul 2;16:4515-4526. doi: 10.2147/IJN.S313673. eCollection 2021.

Abstract

INTRODUCTION

Neuroregeneration is a major challenge in neuroscience for treating degenerative diseases and for repairing injured nerves. Numerous studies have shown the importance of physical stimulation for neuronal growth and development, and here we report an approach for the physical guidance of neuron orientation and neurite growth using superparamagnetic iron oxide (SPIO) nanoparticles and magnetic fields (MFs).

METHODS

SPIO nanoparticles were synthesized by classic chemical co-precipitation methods and then characterized by transmission electron microscope, dynamic light scattering, and vibrating sample magnetometer. The cytotoxicity of the prepared SPIO nanoparticles and MF was determined using CCK-8 assay and LIVE/DEAD assay. The immunofluorescence images were captured by a laser scanning confocal microscopy. Cell migration was evaluated using the wound healing assay.

RESULTS

The prepared SPIO nanoparticles showed a narrow size distribution, low cytotoxicity, and superparamagnetism. SPIO nanoparticles coated with poly-L-lysine could be internalized by spiral ganglion neurons (SGNs) and showed no cytotoxicity at concentrations less than 300 µg/mL. The neurite extension of SGNs was promoted after internalizing SPIO nanoparticles with or without an external MF, and this might be due to the promotion of growth cone development. It was also confirmed that SPIO can regulate cell migration and can direct neurite outgrowth in SGNs preferentially along the direction imposed by an external MF.

CONCLUSION

Our results provide a fundamental understanding of the regulation of cell behaviors under physical cues and suggest alternative treatments for sensorineural hearing loss caused by the degeneration of SGNs.

摘要

简介

神经再生是神经科学领域的一个主要挑战,它可以用于治疗退行性疾病和修复受损的神经。许多研究表明物理刺激对于神经元的生长和发育非常重要,在这里我们报告了一种使用超顺磁氧化铁(SPIO)纳米粒子和磁场(MF)物理引导神经元取向和神经突生长的方法。

方法

通过经典的化学共沉淀法合成 SPIO 纳米粒子,然后通过透射电子显微镜、动态光散射和振动样品磁强计对其进行表征。使用 CCK-8 测定法和 LIVE/DEAD 测定法测定了制备的 SPIO 纳米粒子和 MF 的细胞毒性。通过激光扫描共聚焦显微镜捕获免疫荧光图像。使用划痕愈合试验评估细胞迁移。

结果

所制备的 SPIO 纳米粒子具有较窄的粒径分布、低细胞毒性和超顺磁性。用聚-L-赖氨酸包被的 SPIO 纳米粒子可以被螺旋神经节神经元(SGNs)内化,并且在浓度小于 300μg/mL 时没有细胞毒性。在有或没有外部 MF 的情况下,内化 SPIO 纳米粒子后 SGNs 的神经突延伸得到促进,这可能是由于生长锥发育的促进。还证实 SPIO 可以调节细胞迁移,并可以沿着外部 MF 施加的方向优先引导 SGNs 中的神经突生长。

结论

我们的结果提供了对物理线索下细胞行为调节的基本理解,并为 SGN 退化引起的感音神经性听力损失提供了替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9464/8259836/85439e0f9b49/IJN-16-4515-g0001.jpg

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