Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil.
Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Front Immunol. 2020 Oct 28;11:591563. doi: 10.3389/fimmu.2020.591563. eCollection 2020.
Crotoxin (CTX), the main neurotoxin from snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 μg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.
响尾蛇毒素（CTX）是蛇毒中的主要神经毒素，具有抗炎、免疫调节和镇痛作用。然而，CTX 诱导的毒性可能会影响其应用。在这种情况下，使用纳米颗粒（如纳米结构介孔硅 SBA-15）作为载体可能成为提高 CTX 安全性的一种可行方法。在这里，我们确定了 SBA-15 对实验性自身免疫性脑脊髓炎（EAE）中 CTX 相关神经炎症和免疫调节特性的益处，EAE 是多发性硬化症的动物模型，可复制人类中观察到的几种组织病理学和免疫学特征。我们表明，与 CTX 治疗的 EAE 组相比，单次给予 CTX：SBA-15（54μg/kg）可更有效地减轻疼痛并改善 EAE 动物的临床评分（运动障碍）；从而改善疾病结局。有趣的是，CTX：SBA-15，而不是未缀合的 CTX，可预防 EAE 引起的萎缩和肌肉功能丧失。进一步支持免疫机制，CTX：SBA-15 治疗可减少外周 Th17 细胞的募集和增殖，并降低 EAE 动物脊髓中 IL-17 的表达和神经胶质细胞的激活，与 CTX 治疗的 EAE 组相比。最后，CTX：SBA-15，但不是未缀合的 CTX，可防止 EAE 引起的中枢神经系统细胞浸润。这些结果提供了证据，表明 SBA-15 可在 EAE 模型中最大限度地提高 CTX 的免疫调节和抗炎作用；因此，表明 SBA-15 有可能提高 CTX 在治疗多发性硬化症中的有效性。
