Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, Jiangxi, China.
Key Laboratory for Research and Utilization of Characteristic Biological Resources in Southern Yunnan, College of Biological and Agricultural Sciences, Honghe University, Mengzi 661199, China.
ACS Appl Mater Interfaces. 2024 Jun 5;16(22):28041-28055. doi: 10.1021/acsami.4c01453. Epub 2024 May 20.
Bacterial infection poses a significant challenge to wound healing and skin regeneration, leading to substantial economic burdens on patients and society. Therefore, it is crucial to promptly explore and develop effective methodologies for bacterial infections. Herein, we propose a novel approach for synthesizing nanostructures based on antisense oligonucleotides (ASOs) through the coordination-driven self-assembly of Zn with ASO molecules. This approach aims to provide effective synergistic therapy for chronic wound infections caused by (). The resulting hybrid nanoparticles successfully preserve the structural integrity and biological functionalities of ASOs, demonstrating excellent ASO encapsulation efficiency and bioaccessibility. antibacterial experiments reveal that Zn-ASO NPs exhibit antimicrobial properties against , , and . This antibacterial ability is attributed to the high concentration of metal zinc ions and the generation of high levels of reactive oxygen species. Additionally, the ftsZ-ASO effectively inhibits the expression of the ftsZ gene, further enhancing the antimicrobial effect. antibacterial assays demonstrate that the Zn-ASO NPs promote optimal skin wound healing and exhibit favorable biocompatibility against infections, resulting in a residual infected area of less than 8%. This combined antibacterial strategy, which integrates antisense gene therapy and metal-coordination-directed self-assembly, not only achieves synergistic and augmented antibacterial outcomes but also expands the horizons of ASO coordination chemistry. Moreover, it addresses the gap in the antimicrobial application of metal-coordination ASO self-assembly, thereby advancing the field of ASO-based therapeutic approaches.
细菌感染对伤口愈合和皮肤再生构成重大挑战，给患者和社会带来巨大的经济负担。因此，及时探索和开发有效的细菌感染治疗方法至关重要。在此，我们提出了一种基于锌与反义寡核苷酸（ASO）分子配位自组装合成纳米结构的新方法。该方法旨在为 （）引起的慢性伤口感染提供有效的协同治疗。所得的杂化纳米颗粒成功地保持了 ASO 的结构完整性和生物学功能，表现出优异的 ASO 包封效率和生物可及性。抗菌实验表明，Zn-ASO NPs 对 、 、 具有抗菌性能。这种抗菌能力归因于高浓度的金属锌离子和高水平的活性氧的产生。此外，ftsZ-ASO 有效地抑制了 ftsZ 基因的表达，进一步增强了抗菌效果。抗菌实验表明，Zn-ASO NPs 促进了最佳的皮肤伤口愈合，并对 感染表现出良好的生物相容性，感染残留面积小于 8%。这种结合了反义基因治疗和金属配位导向自组装的协同抗菌策略，不仅实现了协同增强的抗菌效果，还扩展了 ASO 配位化学的应用范围。此外，它解决了金属配位 ASO 自组装在抗菌应用方面的差距，从而推动了基于 ASO 的治疗方法的发展。
