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基于 NEO100 的制剂经鼻腔给予 miR133b 可诱导脊髓损伤小鼠产生修复反应。

Intranasal Delivery of miR133b in a NEO100-Based Formulation Induces a Healing Response in Spinal Cord-Injured Mice.

机构信息

Department of Neurological Surgery, University of Southern California, Los Angeles, CA 90033, USA.

Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.

出版信息

Cells. 2023 Mar 18;12(6):931. doi: 10.3390/cells12060931.

DOI:10.3390/cells12060931
PMID:36980272
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10047048/
Abstract

Despite important advances in the pre-clinical animal studies investigating the neuroinhibitory microenvironment at the injury site, traumatic injury to the spinal cord remains a major problem with no concrete response. Here, we examined whether (1) intranasal (IN) administration of miR133b/Ago2 can reach the injury site and achieve a therapeutic effect and (2) NEO100-based formulation of miR133b/Ago2 can improve effectiveness. 24 h after a cervical contusion, C57BL6 female mice received IN delivery of miR133b/Ago2 or miR133b/Ago2/NEO100 for 3 days, one dose per day. The pharmacokinetics of miR133b in the spinal cord lesion was determined by RT-qPCR. The role of IN delivery of miR133b on motor function was assessed by the grip strength meter (GSM) and hanging tasks. The activity of miR133b at the lesion site was established by immunostaining of fibronectin 1 (FN1), a miR133b target. We found that IN delivery of miR133b/Ago2 (1) reaches the lesion scar and co-administration of miR133b with NEO100 facilitated the cellular uptake; (2) enhanced the motor function and addition of NEO100 potentiated this effect and (3) targeted FN1 expression at the lesion scar. Our results suggest a high efficacy of IN delivery of miR133b/Ago2 to the injured spinal cord that translates to improved healing with NEO100 further potentiating this effect.

摘要

尽管在研究损伤部位神经抑制微环境的临床前动物研究中取得了重要进展，但脊髓创伤仍然是一个主要问题，尚无具体对策。在这里，我们研究了（1）经鼻（IN）给予 miR133b/Ago2 是否可以到达损伤部位并实现治疗效果，以及（2）基于 NEO100 的 miR133b/Ago2 制剂是否可以提高疗效。在颈椎挫伤后 24 小时，C57BL6 雌性小鼠接受 IN 递送 miR133b/Ago2 或 miR133b/Ago2/NEO100，每天一次，共 3 天。通过 RT-qPCR 确定 miR133b 在脊髓损伤中的药代动力学。通过握力计（GSM）和悬挂任务评估 IN 递送 miR133b 对运动功能的作用。通过免疫染色纤维连接蛋白 1（FN1）（miR133b 的靶标）确定 miR133b 在损伤部位的活性。我们发现，IN 递送 miR133b/Ago2（1）到达损伤瘢痕，并且 miR133b 与 NEO100 联合给药促进了细胞摄取；（2）增强了运动功能，并且添加 NEO100 增强了这种作用，（3）靶向损伤瘢痕中的 FN1 表达。我们的结果表明，IN 递送 miR133b/Ago2 对受伤脊髓具有很高的疗效，与 NEO100 联合使用可进一步增强这种作用，从而改善愈合效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/d504f26b54d4/cells-12-00931-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/7644d61997be/cells-12-00931-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/24eba01c01c2/cells-12-00931-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/d504f26b54d4/cells-12-00931-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/7644d61997be/cells-12-00931-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/ad87967d1f22/cells-12-00931-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/88c3073266cc/cells-12-00931-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/e6e33cb2f1ba/cells-12-00931-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/3a09d531e8f1/cells-12-00931-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/c7c09a968e3a/cells-12-00931-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/24eba01c01c2/cells-12-00931-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/0fc7566f8bc6/cells-12-00931-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f91/10047048/d504f26b54d4/cells-12-00931-g009.jpg

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