Denman Desirée S, Dalhaimer Paul
Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, USA.
Nanoscale. 2025 Oct 9;17(39):22594-22605. doi: 10.1039/d5nr02301g.
The components of nanoparticles can trigger the production of antibodies in patients and in model mammals such as mice. We focus on antibodies made against poly-ethylene-glycol (PEG), the most common polymer component of nanoparticles. Humans are frequently exposed to free PEG in processed foods, cosmetics, and over-the-counter drugs. These PEG-containing products trigger varying amounts of anti-PEG antibody production in consumers. In addition to consumer product usage, human exposure to PEG was greatly increased when millions were vaccinated with SARS-CoV-2 vaccine nanoparticles, which contained a PEGylated lipid. Thus, the chances of humans having anti-PEG antibodies is high and the ramifications of the presence of such antibodies must be addressed. The resulting antibodies could bind and negatively affect PEG-containing nanoparticles that are subsequently administered to patients. For example, a patient administered the PEGylated liposome DOXIL could have "pre-existing" anti-PEG antibodies from cosmetic products. The anti-PEG antibodies could bind the PEG component of DOXIL and take it to professional phagocytes. This would greatly reduce its ability to localize to cancer cells. In this review, we discuss the possible mechanisms by which PEG could generate immunoglobulin M (IgM) and how PEG could trigger a stronger and more mechanistically complex immunoglobulin G (IgG) response. We assess PEG-antibody binding. We discuss the various mechanisms by which PEG-containing nanoparticles may bind immune cells. We address gaps in our knowledge of the mechanisms of anti-PEG antibody formation. We discuss strategies for determining whether PEG triggers antibody production and how strong the antibody will interact with the PEG.
纳米颗粒的成分可在患者以及小鼠等模型哺乳动物体内引发抗体产生。我们重点关注针对聚乙二醇（PEG）产生的抗体，PEG是纳米颗粒中最常见的聚合物成分。人类经常在加工食品、化妆品和非处方药中接触到游离的PEG。这些含PEG的产品会在消费者体内引发不同程度的抗PEG抗体产生。除了消费产品的使用，当数百万人接种含有聚乙二醇化脂质的新冠病毒疫苗纳米颗粒时，人类对PEG的接触大幅增加。因此，人类拥有抗PEG抗体的可能性很高，必须解决此类抗体存在的后果。产生的抗体可能会结合并对随后给予患者的含PEG纳米颗粒产生负面影响。例如，接受聚乙二醇化脂质体阿霉素（DOXIL）治疗的患者可能因化妆品而产生“预先存在”的抗PEG抗体。抗PEG抗体可能会结合DOXIL的PEG成分并将其带到专业吞噬细胞。这将大大降低其定位于癌细胞的能力。在这篇综述中，我们讨论了PEG可能产生免疫球蛋白M（IgM）的可能机制，以及PEG如何引发更强且机制更复杂的免疫球蛋白G（IgG）反应。我们评估PEG-抗体结合情况。我们讨论了含PEG纳米颗粒可能结合免疫细胞的各种机制。我们指出了我们在抗PEG抗体形成机制知识方面的空白。我们讨论了确定PEG是否触发抗体产生以及抗体与PEG相互作用强度的策略。
