Fu Yifei, Kolanthai Elayaraja, Neal Craig J, Kumar Udit, Zgheib Carlos, Liechty Kenneth W, Seal Sudipta
Advanced Materials Processing and Analysis Center, Dept. of Materials Science and Engineering, University of Central Florida, Orlando, FL 32826, USA.
Laboratory for Fetal and Regenerative Biology, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ 85721, USA.
Nanomaterials (Basel). 2022 Dec 9;12(24):4389. doi: 10.3390/nano12244389.
In general, wound healing is a highly ordered process, with distinct phases of inflammation, proliferation, and remodeling. However, among diabetic patients, the progression through these phases is often impeded by increased level of oxidative stress and persistent inflammation. Our previous studies demonstrated that cerium oxide nanoparticles (CNPs) conjugated with therapeutic microRNA146a (miR146a) could effectively enhance wound healing by targeting the NFκB pathway, reducing oxidative stress and inflammation. In the present study, we consider the potential effects of nanomaterial surface-faceting and morphology on the efficacy of miRNA delivery. Compared with octahedral-CNPs and cubic-CNPs, rod-CNPs exhibited higher loading capacity. In addition, in comparing the influence of particle morphology on wound healing efficacy, several markers for bioactivity were evaluated and ascribed to the combined effects of the gene delivery and reactive oxygen species (ROS) scavenging properties. In the cellular treatment study, rod-CNP-miR146a displayed the greatest miR146a delivery into cells. However, the reduction of IL-6 was only observed in the octahedral-CNP-miR146a, suggesting that the efficacy of the miRNA delivery is a result of the combination of various factors. Overall, our results give enlightenments into the relative delivery efficiency of the CNPs with different morphology enhancing miRNA delivery efficacy.
一般来说,伤口愈合是一个高度有序的过程,具有炎症、增殖和重塑等不同阶段。然而,在糖尿病患者中,这些阶段的进展常常受到氧化应激水平升高和持续炎症的阻碍。我们之前的研究表明,与治疗性微小RNA146a(miR146a)偶联的氧化铈纳米颗粒(CNPs)可通过靶向NFκB途径、降低氧化应激和炎症来有效促进伤口愈合。在本研究中,我们考虑了纳米材料的表面刻面和形态对miRNA递送效果的潜在影响。与八面体CNPs和立方体CNPs相比,棒状CNPs表现出更高的负载能力。此外,在比较颗粒形态对伤口愈合效果的影响时,评估了几种生物活性标志物,并将其归因于基因递送和活性氧(ROS)清除特性的综合作用。在细胞治疗研究中,棒状CNP-miR146a向细胞内递送miR146a的能力最强。然而,仅在八面体CNP-miR146a中观察到IL-6的减少,这表明miRNA递送的效果是多种因素共同作用的结果。总体而言,我们的结果为不同形态的CNPs增强miRNA递送效果的相对递送效率提供了启示。