Abstract

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Title:: siRNA delivered by nanogels facilitates peripheral nerve repair through inhibiting ferroptosis in Schwann cells

Author(s):: YANG Jun1; 2; HUANG Xinlin3; QIN Hanjun4; XIE Siyuan5; ZHU Yuhua6; WU Jun7; 1. Department of Orthopedics, the 74th Group Army Hospital of PLA (formerly, the 421st Hospital of PLA), Guangzhou 510318, China 2. Department of Orthopedic Trauma, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 3. Department of Joint and Bone Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 4. Department of Orthopedic Trauma, Shenzhen Peoples Hospital (the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen 518020, China 5. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China 6. Department of Spinal Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 7. Physical Examination Center of the Outpatient Department, the 74th Group Army Hospital of PLA (formerly, the 421st Hospital of PLA), Guangzhou 510318, China

Keywords:: Keywords: peripheral nerve injury Schwann cell ferroptosis nanogel siRNA targeted therapy

Abstract:: Abstract: Objective To investigate the mechanism of Schwann cell death after peripheral nerve injury (PNI), and to inhibit Schwann cell death by nanogel-delivered siRNA. Methods The transcriptome data of PNI in GEO database were downloaded for data processing, followed by difference analysis, GO functional enrichment analysis, ferroptosis pathway identification, and target gene screening. The differences of target genes were verified through protein imprinting and qPCR experiment. The physical and biological properties of self-assembled tannic acid (TA)-siRNA nanogels were identified by Tyndall effect, particle size and potential measurements, phagocytosis assay, cytoskeleton staining, and CCK-8 cell viability assay. The effectiveness of TA-siRNA nanogel in inhibiting ferroptosis in Schwann cells was verified by scratch experiment, immunofluorescence staining, protein imprinting, and qPCR experiment. Results After PNI, obvious ferroptosis was observed in Schwann cells, and Bex1 was identified as the key gene regulating ferroptosis in Schwann cells. With excellent physical and biological properties, TA-siRNA nanogel could successfully carry siRNA into damaged Schwann cells, and silence their ferroptosis genes, thus effectively inhibiting ferroptosis after Schwann cell damage. Conclusion Nanogel-delivered siRNA can inhibit ferroptosis in Schwann cells, providing a new direction for PNI treatment.