Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-07-15 , DOI: 10.1007/s13346-022-01206-6 Rob J Vandebriel 1 , Christopher A W David 2 , Jolanda P Vermeulen 1 , Neill J Liptrott 2
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Nanoparticles including nanomedicines are known to be recognised by and interact with the immune system. As these interactions may result in adverse effects, for safety evaluation, the presence of such interactions needs to be investigated. Nanomedicines in particular should not unintendedly interact with the immune system, since patient’s exposure is not minimised as in the case of ‘environmental’ nanoparticles, and repeated exposure may be required. NLRP3 inflammasome activation and dendritic cell (DC) maturation are two types of immune mechanisms known to be affected by nanoparticles including nanomedicines. NLRP3 inflammasome activation results in production of the pro-inflammatory cytokines IL-1β and IL-18, as well as a specific type of cell death, pyroptosis. Moreover, chronic NLRP3 inflammasome activation has been related to several chronic diseases. Upon maturation, DC activate primary T cells; interference with this process may result in inappropriate activation and skewing of the adaptive immune response. Here, we evaluated the effect of two nanomedicines, representing nanostructured lipid carriers and polymers, on these two assays. Moreover, with a view to possible future standardisation and regulatory application, these assays were subject to an inter-laboratory comparison study using common SOPs. One laboratory performed three independent NLRP3 inflammasome activation experiments, while the other performed a single experiment. Two laboratories each performed three independent DC maturation experiments. While the nanostructured lipid carrier only showed marginal effects, the polymers showed major cytotoxicity. No evidence for inflammasome activation or DC maturation was demonstrated. Intra- and inter-laboratory comparison showed clearly reproducible results.
Graphical abstract
中文翻译：
NLRP3 炎性体激活试验和树突状细胞成熟试验的实验室间比较使用纳米结构脂质载体和聚合物纳米药物，作为示例
已知包括纳米药物在内的纳米颗粒被免疫系统识别并与免疫系统相互作用。由于这些相互作用可能导致不利影响，因此为了进行安全性评估，需要调查这种相互作用的存在。尤其是纳米药物不应无意中与免疫系统相互作用，因为患者的暴露不会像“环境”纳米粒子那样最小化，并且可能需要重复暴露。NLRP3 炎性体激活和树突状细胞 (DC) 成熟是已知受包括纳米药物在内的纳米颗粒影响的两种免疫机制。NLRP3 炎性体激活导致促炎细胞因子 IL-1β 和 IL-18 的产生，以及特定类型的细胞死亡，即细胞焦亡。而且，慢性 NLRP3 炎性体激活与几种慢性疾病有关。成熟后，DC 激活原代 T 细胞；干扰这一过程可能会导致适应性免疫反应的不适当激活和偏斜。在这里，我们评估了代表纳米结构脂质载体和聚合物的两种纳米药物对这两种测定的影响。此外，考虑到未来可能的标准化和监管应用，这些化验需要使用通用 SOP 进行实验室间比较研究。一个实验室进行了三个独立的 NLRP3 炎性体激活实验，而另一个实验室进行了一个实验。两个实验室各自进行了三个独立的直流成熟实验。虽然纳米结构的脂质载体只显示出边际效应，聚合物显示出主要的细胞毒性。没有证据表明炎症小体激活或 DC 成熟。实验室内和实验室间比较显示出明显可重复的结果。
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