Assessing the bio-stability of microRNA-146a conjugated nanoparticles via electroanalysis.

Assessing the bio-stability of microRNA-146a conjugated nanoparticles via electroanalysis.
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DOI:
10.1039/d2na00600f
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发表时间:
2022-12-20
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
材料科学3区
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--
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糖尿病患者的数量在全球范围内不断增加,并且与临床发病率的显著情况相关。活性氧(ROS)和促炎细胞因子的增加与糖尿病伤口的发病机制有关,并导致愈合的显着延迟。我们之前的研究已经显示了与抗炎microRNA miR 146 a(CNP-miR 146 a)缀合的氧化铈纳米颗粒(CNP)制剂增强糖尿病伤口愈合的能力。观察到的治疗活性超过了单个缀合物组分(单独的CNP和miR 146 a)的组合功效,表明协同效应。目前的研究评估了先前观察到的增强的活性是否来自增加的药剂递送(简单的纳米载体活性)或对CNP-miR 146 a制剂(功能性生物活性纳米材料)具有特异性。与miR 146 a缀合的金(生物活性的,金属)和二氧化硅(生物惰性的,氧化物)纳米颗粒(AuNP和SiO2 NP)的比较在H2 O2的存在下进行,H2 O2作为糖尿病伤口环境中存在的高水平ROS的类似物。电化学研究、材料表征和化学测定显示AuNP-miR 146 a与H2 O2的有限相互作用和SiO2 NP-miR 146 a随时间的不稳定性。相比之下,CNP-miR 146 a显示出化学稳定性和持久的ROS清除能力,这支持了我们先前的结果。此外,确定了CNP在长时间暴露于H2 O2下保护miR 146 a免受氧化损伤,而AuNP和SiO2 NP显示出无效。总的来说,这些结果增强了CNP稳定和保护miRNA的能力,同时表现出强大的抗氧化特性,表明在相关的早期研究中观察到的治疗活性并不限于简单的纳米载体功能。通过详细的电分析研究了与不同纳米颗粒缀合的microRNA-146 a在高氧化应激存在下的稳定性。
The number of diabetics is increasing worldwide and is associated with significant instances of clinical morbidity. Increased amounts of reactive oxygen species (ROS) and proinflammatory cytokines are associated with the pathogenesis of diabetic wounds and result in a significant delay in healing. Our previous studies have shown the ability of a cerium oxide nanoparticle (CNP) formulation conjugated with the anti-inflammatory microRNA miR146a (CNP-miR146a) to enhance the healing of diabetic wounds. The observed therapeutic activity exceeded the combined efficacies of the individual conjugate components (CNPs and miR146a alone), suggesting a synergistic effect. The current study evaluates whether the previously observed enhanced activity arises from increased agent delivery (simple nanocarrier activity) or is specific to the CNP-miR146a formulation (functional, bio-active nanomaterial). Comparison with miR146a conjugated gold (bioactive, metal) and silica (bioinert, oxide) nanoparticles (AuNPs and SiO2NPs) was performed in the presence of H2O2, as an analogue to the high levels of ROS present in the diabetic wound environment. Electrochemical studies, materials characterization, and chemical assays showed limited interaction of AuNP-miR146a with H2O2 and instability of SiO2NP-miR146a over time. In contrast, and in support of our prior results, CNP-miR146a displayed chemical stability and persistent ROS scavenging ability. Furthermore, it was determined that CNPs protect miR146a from oxidative damage under prolonged exposure to H2O2, whereas AuNPs and SiO2NPs were shown to be ineffective. Overall, these results reinforce the ability of CNPs to stabilize and protect miRNA while exhibiting robust antioxidant properties, suggesting that therapeutic activity observed in related earlier studies is not limited to a facile nanocarrier function. The stability of microRNA-146a conjugated with different nanoparticles in the presence of high oxidative stress was investigated through detailed electroanalysis.
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