Application of silver nanoparticles for improving motor recovery after spinal cord injury via reduction of pro-inflammatory M1 macrophages
Jie Lin,
Peikai Chen,
Zhijia Tan,
Yi Sun,
Wai Kit Tam,
Di Ao,
Wei Shen,
Victor Yu-Leong Leung,
Kenneth Man Chee Cheung,
Michael Kai Tsun To
Affiliations
Jie Lin
Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China; Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Peikai Chen
Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China
Zhijia Tan
Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China
Yi Sun
Department of Sports Medicine, Peking University-Shenzhen Hospital, Shenzhen, Guangdong, 518034, China
Wai Kit Tam
Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Di Ao
Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Wei Shen
Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Victor Yu-Leong Leung
Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Corresponding author. Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Kenneth Man Chee Cheung
Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China; Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Corresponding author. Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China
Michael Kai Tsun To
Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China; Department of Orthopaedics & Traumatology, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Corresponding author. Department of Orthopaedics & Traumatology, The University of Hong Kong Shenzhen Hospital, School of Clinical Medicine, The University of Hong Kong, Shenzhen, Guangdong, 518053, China
Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.
