Cell Screening Facility for Personalized Medicine, Laboratory for Neurodegenerative Diseases and Personalized Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Nanotechnology. 2011 Dec 9;22(49):494016. doi: 10.1088/0957-4484/22/49/494016. Epub 2011 Nov 21.
Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering.
基于脂质的纳米颗粒（LNPs）被广泛用于药物和核酸的递释。尽管大多数 LNPs 被认为是安全的，但文献中关于其潜在细胞毒性的证据令人困惑。此外，人们对细胞在受到细胞毒性损伤后的恢复过程知之甚少。我们之前研究了具有不同表面电荷（阳离子、阴离子、中性）的常见 LNPs 的全身效应，结果表明，带正电荷的 LNPs((+)LNPs) 通过作为 Toll 样受体 4 的激动剂在免疫细胞上发挥作用，激活促炎细胞因子并诱导干扰素反应。在这项研究中，我们专注于暴露于 LNPs 的人成纤维细胞的反应及其细胞恢复过程。为此，我们使用基于图像的高通量分析（HCA）。使用这种策略，我们能够同时在几个细胞内参数中显示，成纤维细胞可以从(+)LNPs 的细胞毒性作用中恢复。HCA 的使用为理解细胞反应和纳米毒性开辟了新途径，并且可能成为筛选用于药物递送和组织工程的安全材料的有价值工具。
