Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, PR China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, PR China.
Adv Drug Deliv Rev. 2023 Sep;200:115044. doi: 10.1016/j.addr.2023.115044. Epub 2023 Aug 2.
During the last two decades, an increasing number of reports have pointed out that the immunogenicity of polyethylene glycol (PEG) may trigger accelerated blood clearance (ABC) and hypersensitivity reaction (HSR) to PEGylated nanoparticles, which could make PEG modification counterproductive. These phenomena would be detrimental to the efficacy of the load and even life-threatening to patients. Consequently, further elucidation of the interplay between PEGylated nanoparticles and the blood immune system will be beneficial to developing and applying related formulations. Many groups have worked to unveil the relevance of structural factors, dosing schedule, and other factors to the ABC phenomenon and hypersensitivity reaction. Interestingly, the results of some reports seem to be difficult to interpret or contradict with other reports. In this review, we summarize the physiological mechanisms of PEG-specific immune response. Moreover, we speculate on the potential relationship between the induction phase and the effectuation phase to explain the divergent results in published reports. In addition, the role of nanoparticle-associated factors is discussed based on the classification of the action phase. This review may help researchers to develop PEGylated nanoparticles to avoid unfavorable immune responses based on the underlying mechanism.
在过去的二十年中，越来越多的报告指出，聚乙二醇（PEG）的免疫原性可能引发对聚乙二醇化纳米颗粒的加速血液清除（ABC）和过敏反应（HSR），这可能使 PEG 修饰适得其反。这些现象将对负载的疗效产生不利影响，甚至对患者造成生命威胁。因此，进一步阐明聚乙二醇化纳米颗粒与血液免疫系统之间的相互作用将有助于开发和应用相关制剂。许多研究小组致力于揭示结构因素、给药方案和其他因素与 ABC 现象和过敏反应的相关性。有趣的是，一些报告的结果似乎难以解释或与其他报告相矛盾。在这篇综述中，我们总结了 PEG 特异性免疫反应的生理机制。此外，我们推测诱导阶段和实现阶段之间的潜在关系，以解释已发表报告中的分歧结果。此外，还根据作用阶段的分类讨论了纳米颗粒相关因素的作用。这篇综述可能有助于研究人员根据潜在机制开发避免不利免疫反应的聚乙二醇化纳米颗粒。
