通过四面体框架核酸递送 Microrna-124 促进软骨再生改善骨关节炎,Advanced Functional Materials

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通过四面体框架核酸递送 Microrna-124 促进软骨再生改善骨关节炎
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-07-09 , DOI: 10.1002/adfm.202305558
Sirong Shi ₁ , Tianyu Chen ₁ , Weitong Lu ₁ , Yang Chen _{2,

3} , Dexuan Xiao ₁ , Yunfeng Lin ₁

Affiliation

MicroRNA (miRNA) 调节涉及多种疾病的多种生理和病理过程，包括骨关节炎 (OA)。OA 是最常见的全身肌肉骨骼疾病，其特征是关节软骨不可逆的进行性破坏。补充外源 miRNA 可能是一种有前景的 OA 治疗方法，其中 miRNA-124 (miR-124) 因其抗炎能力而成为主要候选者；然而，迫切需要一种有效的药物递送系统来增强 miR-124 的稳定性和进入软骨细胞的能力。为此，四面体框架核酸（tFNA）自组装3D DNA纳米结构具有优越的固有生物相容性、多功能性、无与伦比的可编辑性和强大的细胞内化能力。在本研究中，成功合成了携带一或三个miR-124（T-miR1或T-miR3）的tFNA。T-miR3 大部分通过 IL-1β 诱导的炎症软骨细胞被吸收。凭借活性氧的清除能力和抑制炎症的 miR-124 释放行为，T-miR3 在体外可有效保护软骨细胞免受 IL-1β 损伤。此外，T-miR3通过抑制软骨细胞凋亡、平滑软骨表面、抑制细胞外基质降解、增加滑膜厚度来有效预防OA进展，有效保护体内关节软骨，说明T-miR3在OA治疗中的治疗能力。这项研究为临床治疗 OA 提供了实验证据和新的治疗策略。

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Amelioration of Osteoarthritis via Tetrahedral Framework Nucleic Acids Delivering Microrna-124 for Cartilage Regeneration

MicroRNAs (miRNAs) regulate several physiological and pathological processes involved in various diseases, including osteoarthritis (OA). OA is the most common global musculoskeletal disorder, characterized by the irreversible progressive destruction of articular cartilage. Supplementation with exogenous miRNAs may represent a promising therapeutic OA treatment, with miRNA-124 (miR-124) being a prime candidate for its anti-inflammatory ability; however, an effective drug delivery system is urgently required to enhance miR-124 stability and capacity to enter chondrocytes. To this end, tetrahedral framework nucleic acids’ (tFNAs) self-assembled 3D DNA nanostructures possess superior inherent biocompatibility, versatile functionality, unsurpassed editability, and strong cellular internalization ability. In this study, tFNAs carrying one or three miR-124 (T-miR1 or T-miR3) are successfully synthesized. T-miR3 is largely absorbed via induced inflammatory chondrocytes by IL-1β. With reactive oxygen species’ scavenging ability and inflammation-suppressive miR-124 release behavior, T-miR3 efficiently protects chondrocytes against IL-1β injury in vitro. Additionally, T-miR3 effectively prevents OA progression by inhibiting chondrocyte apoptosis, smoothing cartilage surfaces, suppressing extracellular matrix degradation, and increasing synovial thickness, effectively protecting in vivo articular cartilage, and illustrating the therapeutic ability of T-miR3 in OA treatment. This study provides experimental evidence and novel therapeutic strategies for OA treatment in the clinical setting.

更新日期：2023-07-09

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