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Abstract：
In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction. Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases. The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects. Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids. In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis. The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries. This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids. The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper. Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis. Further clinical studies are required to confirm the findings in cell- and animal-based experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization. It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.
摘要：
近年来,随着核酸药物抗脓毒症及其相关器官功能障碍的成功，基因治疗成为可能。基于核酸的治疗学，如小干扰RNA（siRNA），microRNAs(miRNAs),信使RNA（mRNA），和质粒DNA（pDNAs）保证治疗以前不可用的疾病。基于核酸的治疗败血症的优势在于纳米载体的发展，实现靶向和受控的基因递送，以提高疗效，副作用最小。捕获到纳米载体中还改善了裸核酸的不良细胞摄取。在这项研究中,我们讨论了用于核酸递送的纳米颗粒治疗与脓毒症相关的过度炎症和细胞凋亡的最新技术。通过物理化学性质修饰和配体缀合的纳米粒子的优化设计可以靶向特定的器官，例如肺，心,肾,和肝脏-减轻多个败血症相关的器官损伤。这篇综述重点介绍了用于制造抗脓毒症纳米系统的纳米材料，它们的物理化学特征，基于核酸的治疗对脓毒症的机制，以及提高核酸治疗效率的潜力。本文总结了目前与纳米颗粒核酸在脓毒症管理中的应用相关的研究。值得注意的是,纳米治疗核酸的潜在应用为治疗脓毒症提供了新的策略.需要进一步的临床研究来证实细胞和动物实验中的发现。大规模生产的能力和纳米颗粒产品的再现性对于商业化也是至关重要的。预计未来将针对基于核酸的纳米治疗剂研究许多抗脓毒症的可能性。
