The inability to systemic administration of nanoparticles, particularly cationic nanoparticles, has been a significant barrier to their clinical translation due to toxicity concerns. Understanding the in vivo behavior of cationic lipids is crucial, given their potential impact on critical biological components such as immune cells and hematopoietic stem cells (HSC). These cells are essential for maintaining the body's homeostasis, and their interaction with cationic lipids is a key factor in determining the safety and efficacy of these nanoparticles. In this study, we focused on the cytotoxic effects of cationic lipid/DNA complexes (CLN/DNA). Significantly, we observed that the most substantial cytotoxic effects, including a marked increase in numbers of long-term hematopoietic stem cells (LT-HSC), occurred 24 h post-CLN/DNA treatment in mice. Furthermore, we found that CLN/DNA-induced HSC expansion in bone marrow (BM) led to a notable decrease in the ability to reestablish blood cell production. Our study provides crucial insights into the interaction between cationic lipids and vital cellular components of the immune and hematopoietic systems.

中文翻译：

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阳离子脂质-DNA复合物对体内免疫细胞和造血细胞的影响

由于毒性问题，纳米颗粒（特别是阳离子纳米颗粒）无法全身给药，一直是其临床转化的重大障碍。鉴于阳离子脂质对免疫细胞和造血干细胞 (HSC) 等关键生物成分的潜在影响，了解阳离子脂质的体内行为至关重要。这些细胞对于维持身体的稳态至关重要，它们与阳离子脂质的相互作用是决定这些纳米颗粒的安全性和有效性的关键因素。在这项研究中，我们重点关注阳离子脂质/DNA 复合物 (CLN/DNA) 的细胞毒性作用。值得注意的是，我们观察到最显着的细胞毒性作用，包括长期造血干细胞 (LT-HSC) 数量的显着增加，发生在小鼠 CLN/DNA 治疗后 24 小时。此外，我们发现 CLN/DNA 诱导的 HSC 在骨髓 (BM) 中的扩增导致重建血细胞生成的能力显着下降。我们的研究为阳离子脂质与免疫和造血系统的重要细胞成分之间的相互作用提供了重要的见解。