Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea.
Theranostics. 2020 Feb 10;10(7):3240-3253. doi: 10.7150/thno.39870. eCollection 2020.
: Of the regulatory microRNAs expressed in the wounded skin, microRNA-21 (miR21) plays a pivotal role in wound repair by stimulating re-epithelialization, an essential feature to facilitate healing and reduce scar formation. Despite their crucial roles in wound healing, synthetic exogenous microRNAs have limited applications owing to the lack of an appropriate delivery system. Herein, we designed an miR21 mimic nanocarrier system using facial amphipathic bile acid-conjugated polyethyleneimines (BA-PEI) for the intracellular and transdermal delivery of synthetic miR21 molecules to accelerate wound repair. : To design miR21 mimic nanocarriers, BA-conjugated PEIs prepared from three different types of BA at molar feed ratios of 1 and 3 were synthesized. The intracellular uptake efficiency of synthetic miR21 mimics was studied using confocal laser scanning microscopy and flow cytometry analysis. The optimized miR21/BA nanocarrier system was used to evaluate the wound healing effects induced by miR21 mimics in human HaCaT keratinocytes and a murine excisional acute wound model . : The cell uptake efficiency of miR21 complexed with BA-conjugated PEI was dramatically higher than that of miR21 complexed with PEI alone. Deoxycholic acid (DA)-modified PEI at a molar feed ratio of 3:1 (DA3-PEI) showed the highest transfection efficiency for miR21 without any increase in toxicity. After effective transdermal and intracellular delivery of miR21/DA3 nanocarriers, miR21 mimics promoted cell migration and proliferation through the post-transcriptional regulation of programmed cell death protein 4 (PDCD4) and matrix metalloproteinases. Thus, miR21 mimic nanocarriers improved both the rate and quality of wound healing, as evident from enhanced collagen synthesis and accelerated wound re-epithelialization. : Our miRNA nanocarrier systems developed using DA3-PEI conjugates may be potentially useful for the delivery of synthetic exogenous miRNAs in various fields.
: 在受伤皮肤中表达的调节 microRNA 中，microRNA-21（miR21）通过刺激再上皮化在伤口修复中发挥关键作用，这是促进愈合和减少疤痕形成的必要特征。尽管它们在伤口愈合中具有重要作用，但由于缺乏合适的递送系统，合成外源性 microRNA 的应用受到限制。在此，我们设计了一种使用面部两亲性胆酸修饰的聚乙烯亚胺（BA-PEI）的 miR21 模拟物纳米载体系统，用于合成 miR21 分子的细胞内和透皮递送来加速伤口修复。: 为了设计 miR21 模拟物纳米载体，我们合成了三种不同类型的 BA 以 1 和 3 的摩尔进料比制备的 BA 修饰的 PEI。使用共聚焦激光扫描显微镜和流式细胞术分析研究了合成 miR21 模拟物的细胞内摄取效率。优化的 miR21/BA 纳米载体系统用于评估 miR21 模拟物在人 HaCaT 角质形成细胞和小鼠急性切除性伤口模型中诱导的伤口愈合效果。: 与单独使用 PEI 相比，与 BA-PEI 复合的 miR21 的细胞摄取效率显着提高。摩尔进料比为 3:1 的去氧胆酸（DA）修饰的 PEI（DA3-PEI）显示出最高的 miR21 转染效率，而毒性没有增加。miR21/DA3 纳米载体有效透皮和细胞内递送后，miR21 模拟物通过程序性细胞死亡蛋白 4（PDCD4）和基质金属蛋白酶的转录后调节促进细胞迁移和增殖。因此，miR21 模拟物纳米载体通过增强胶原合成和加速伤口再上皮化来提高伤口愈合的速度和质量。: 我们使用 DA3-PEI 缀合物开发的 miRNA 纳米载体系统可能在各个领域中对合成外源性 miRNA 的递送具有潜在的用途。
