International Journal of Nanomedicine (Jul 2021)
Neurite Extension and Orientation of Spiral Ganglion Neurons Can Be Directed by Superparamagnetic Iron Oxide Nanoparticles in a Magnetic Field
Abstract
Yangnan Hu,1,* Dan Li,2,* Hao Wei,3,* Shan Zhou,1 Wei Chen,1 Xiaoqian Yan,1 Jaiying Cai,1 Xiaoyan Chen,1 Bo Chen,4 Menghui Liao,1 Renjie Chai,1,5 Mingliang Tang1,5,6 1State 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; 2School of Biology, Food and Environment, Hefei University, Hefei, 230601, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou, 215009, People’s Republic of China; 5Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China; 6Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Medical College, Soochow University, Suzhou, 215000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renjie Chai; Mingliang Tang Email [email protected]; [email protected]: 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.Keywords: physical cues, neurites orientation, hearing loss, cochlear implants, migration