Therapy of spinal cord injury by zinc modified gold nanoclusters via immune-suppressing strategies

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; p. 281
• Main Authors: Lin, Sen, Li, Dan, Zhou, Zipeng, Xu, Chang, Mei, Xifan, Tian, He
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.09.2021; BioMed Central; BMC
• Subjects: Acids; Animals; Antibodies; Apoptosis; Biocompatibility; Bladder; Care and treatment; Cell Survival - drug effects; Central nervous system; Chronic pain; Clusters (Chemistry); Complications; Cytotoxicity; Damage; Design and construction; Dihydrolipoic acid; Drug delivery; Drug delivery systems; Drugs; Effector cells; Enantiomers; Enzyme-linked immunosorbent assay; Gold; Gold - chemistry; Gold nanoclusters; Health aspects; Humans; Immune system; Immunosuppression; Immunosuppressive agents; Inflammation; Lymphocytes - cytology; Lymphocytes - immunology; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Metal Nanoparticles - toxicity; Methods; Mice; Monocytes; Monocytes - cytology; Monocytes - immunology; Monocytes/macrophages; Nanoclusters; Nanomaterials; Nanomedicine; Neurons; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative stress; Pain; Patients; Physiology; Polarization; Polls & surveys; Prediction models; Prognosis; Proteins; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive oxygen species; Reactive Oxygen Species - metabolism; Side effects; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - immunology; Spinal Cord Injuries - pathology; Spinal cord injury; Stereoisomerism; Survival; Therapy; Thioctic Acid - analogs & derivatives; Thioctic Acid - chemistry; Transmission electron microscopy; Urination; Zinc; Zinc - chemistry; China; Oxidative stress; Polarization; Gold nanoclusters; Neurons; Inflammation; Monocytes/macrophages; Spinal cord injury; Apoptosis
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-01035-8

Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Unfortunately, few effective and safe treatments are known to relieve the damages of SCI. Nanomedicines are used for the treatment of SCI with relatively few side effects, but only depending on the delivery of additional drugs, which increase complexity to the treatment. Considering the urgent need for saving SCI patients, it is important to develop promising nanobiotechnology for relieving their pains. The clinical survey was used to investigate SCI patients, thereafter the therapy plan was designed. The receiver-operating characteristics (ROC) curves of the prediction model were built to find symptoms after SCI. The treatment plan (i.e. immunosuppressive strategy) was designed by manufacturing therapies based on gold nanoclusters (AuNCs). The response of the immune cells (macrophages) was studied accordingly. The western blot, reactive oxygen species (ROS) activity assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-qPCR), and immunochemical staining were used for evaluation of the in vivo and in vitro therapeutic effects. We found increased monocytes/macrophages (M/Ms) levels in 114 SCI subjects (44.7% with severe SCI complications) by the clinical survey. Additionally, the enhanced macrophage level was found to be closely related to the walking disorder after SCI. Since macrophages were central effector cells of the immune system, we assumed that the immune-suppressing strategies could be used for SCI therapy. Thereafter, AuNCs were stabilized by dihydrolipoic acid (DHLA) enantiomers (including DL-DHLA, R-DHLA; A racemic mixture (R and S) was denoted as DL; R and S refer to Rectus and Sinister), obtaining DL-DHLA-AuNCs and R-DHLA-AuNCs, respectively. In addition, zinc-modified DL-DHLA and R-DHLA stabilized AuNCs (i.e., DL-DHLA-AuNCs-Zn and R-DHLA-AuNCs-Zn) were investigated. Among these AuNCs, R-DHLA-AuNCs-Zn showed the most remarkable therapeutic effect for promoting the polarization of pro-inflammatory macrophages and reducing neuronal ROS-induced apoptosis and inflammation in vitro and in vivo; the lesion size was decreased and the survival rate of ventral neurons is higher. R-DHLA-AuNCs-Zn have comprehensive therapeutic capabilities, especially the immune-suppressing effects for the therapy of SCI, which is promising to relieve the pain or even recover SCI for the patients.