Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.
Nano Lett. 2021 Mar 24;21(6):2461-2469. doi: 10.1021/acs.nanolett.0c04759. Epub 2021 Mar 9.
Circulating cell-free DNA (cfDNA) released by damaged cells causes inflammation and has been associated with the progression of sepsis. One proposed strategy to treat sepsis is to scavenge this inflammatory circulating cfDNA. Here, we develop a cfDNA-scavenging nanoparticle (NP) that consists of cationic polyethylenimine (PEI) of different molecular weight grafted to zeolitic imidazolate framework-8 (PEI--ZIF) in a simple one-pot process. PEIZIF NPs fabricated using PEI 1800 and PEI 25k but not PEI 600 suppressed cfDNA-induced TLR activation and subsequent nuclear factor kappa B pathway activity. PEI 1800--ZIF NPs showed greater inhibition of cfDNA-associated inflammation and multiple organ injury than naked PEI 1800 (lacking ZIF), and had greater therapeutic efficacy in treating sepsis. These results indicate that PEIZIF NPs acts as a "nanotrap" that improves upon naked PEI in scavenging circulating cfDNA, reducing inflammation, and reversing the progression of sepsis, thus providing a novel strategy for sepsis treatment.
循环无细胞 DNA（cfDNA）是由受损细胞释放的，会引起炎症，并且与脓毒症的进展有关。一种治疗脓毒症的方法是清除这种炎症性循环 cfDNA。在这里，我们开发了一种 cfDNA 清除纳米颗粒（NP），它由不同分子量的阳离子聚乙烯亚胺（PEI）接枝到沸石咪唑骨架-8（PEI-ZIF）上，通过简单的一锅法制备而成。使用 PEI 1800 和 PEI 25k 制备的 PEIZIF NPs 但不是 PEI 600 抑制了 cfDNA 诱导的 TLR 激活和随后的核因子 kappa B 途径活性。PEI 1800-ZIF NPs 比裸露的 PEI 1800（缺乏 ZIF）显示出更强的抑制 cfDNA 相关炎症和多器官损伤的作用，并且在治疗脓毒症方面具有更好的疗效。这些结果表明，PEIZIF NPs 作为一种“纳米陷阱”，在清除循环 cfDNA、减轻炎症和逆转脓毒症进展方面优于裸露的 PEI，从而为脓毒症治疗提供了一种新策略。
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