基于四面体框架核酸的miRNA-124和脑卒中归一肽递送系统：急性缺血性脑卒中的靶向治疗

IF 8.2 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2025-02-12 DOI:10.1021/acsami.5c00507

Guannan Du, Yangxue Yao, Wen Chen, Yunfeng Lin, Yao He, Mi Zhou, Xiaoxiao Cai

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引用次数: 0

摘要

急性缺血性脑卒中（AIS）死亡率高、预后差，且溶栓后缺乏有效的治疗药物。基于microrna的基因治疗是治疗AIS的一种很有前景的方法，但由于靶向效率低、稳定性不理想、细胞摄取不足等挑战，其临床应用受到限制。在本研究中，我们成功开发了一种基于四面体框架核酸（tFNA）的微rna靶向递送系统。这种纳米递送系统在脑卒中归家肽的引导下，有效地靶向并将miRNA124递送到缺血半球。在tFNA的辅助下，miRNA124有效进入细胞并发挥治疗作用。此外，它促进小胶质细胞从促炎M1表型向抗炎M2表型转化，减少神经元凋亡，最终降低梗死面积和死亡率。这些发现为AIS的靶向治疗提供了一个有希望的治疗策略。

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Tetrahedral Framework Nucleic Acid-Based Delivery System for miRNA-124 and Stroke-Homing Peptide: Targeted Therapy for Acute Ischemic Stroke

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Tetrahedral Framework Nucleic Acid-Based Delivery System for miRNA-124 and Stroke-Homing Peptide: Targeted Therapy for Acute Ischemic Stroke

Acute ischemic stroke (AIS) is associated with a high mortality rate and poor prognosis, with a lack of effective therapeutic drugs for post-thrombolytic treatment. MicroRNA-based gene therapy is a promising approach for treating AIS, but its clinical application has been limited due to challenges, such as poor targeting efficiency, unsatisfactory stability, and inadequate cellular uptake. In this study, we successfully developed a microRNA-targeted delivery system based on the tetrahedral framework nucleic acid (tFNA). This nanodelivery system, guided by stroke-homing peptides, effectively targeted and delivered miRNA124 to the ischemic hemisphere. With the assistance of tFNA, miRNA124 efficiently entered cells and exerted therapeutic effects. Additionally, it promoted the transformation of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, reducing neuronal apoptosis and, ultimately, decreasing the infarct size and mortality rate. These findings present a promising therapeutic strategy for the targeted treatment of AIS.

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来源期刊

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.