Nasrullah Mohammad, Meenakshi Sundaram Daniel Nisakar, Claerhout Jillian, Ha Khanh, Demirkaya Erkan, Uludag Hasan
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.
Front Bioeng Biotechnol. 2023 Aug 28;11:1243651. doi: 10.3389/fbioe.2023.1243651. eCollection 2023.
Synthetic nanoparticles (NPs) are non-viral equivalents of viral gene delivery systems that are actively explored to deliver a spectrum of nucleic acids for diverse range of therapies. The success of the nanoparticulate delivery systems, in the form of efficacy and safety, depends on various factors related to the physicochemical features of the NPs, as well as their ability to remain "stealth" in the host environment. The initial cytokine response upon exposure to nucleic acid bearing NPs is a critical component of the host response and, unless desired, should be minimized to prevent the unintended consequences of NP administration. In this review article, we will summarize the most recent literature on cytokine responses to nanoparticulate delivery systems and identify the main factors affecting this response. The NP features responsible for eliciting the cytokine response are articulated along with other factors related to the mode of therapeutic administration. For diseases arising from altered cytokine pathophysiology, attempts to silence the individual components of cytokine response are summarized in the context of different diseases, and the roles of NP features on this respect are presented. We finish with the authors' perspective on the possibility of engineering NP systems with controlled cytokine responses. This review is intended to sensitize the reader with important issues related to cytokine elicitation of non-viral NPs and the means of controlling them to design improved interventions in the clinical setting.
合成纳米颗粒（NPs）是病毒基因传递系统的非病毒等效物，目前正在积极探索其用于递送多种核酸以进行各种治疗。纳米颗粒递送系统在疗效和安全性方面的成功取决于与纳米颗粒物理化学特征相关的各种因素，以及它们在宿主环境中保持“隐身”的能力。暴露于携带核酸的纳米颗粒时的初始细胞因子反应是宿主反应的关键组成部分，除非有此需求，否则应尽量减少以防止纳米颗粒给药产生意外后果。在这篇综述文章中，我们将总结关于纳米颗粒递送系统细胞因子反应的最新文献，并确定影响这种反应的主要因素。阐述了引发细胞因子反应的纳米颗粒特征以及与治疗给药方式相关的其他因素。对于由细胞因子病理生理学改变引起的疾病，在不同疾病背景下总结了沉默细胞因子反应各个成分的尝试，并介绍了纳米颗粒特征在这方面的作用。我们以作者对设计具有可控细胞因子反应的纳米颗粒系统可能性的观点作为结尾。这篇综述旨在使读者关注与非病毒纳米颗粒细胞因子引发相关的重要问题，以及在临床环境中控制这些问题以设计改进干预措施的方法。
