Chen Liyu, Glass Joshua J, De Rose Robert, Sperling Claudia, Kent Stephen J, Houston Zachary H, Fletcher Nicholas L, Rolfe Barbara E, Thurecht Kristofer J
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
ACS Appl Bio Mater. 2018 Sep 17;1(3):756-767. doi: 10.1021/acsabm.8b00220. Epub 2018 Sep 5.
The benefits of nanomedicine may be restricted by hemocompatibility and immunoreactivity problems arising from administration of exogenous materials into the bloodstream. To understand how surface charge influences the interaction of polymeric nanoparticles with blood components, we synthesized three well-defined, charge-varied hyperbranched polymers (HBPs) of similar size and analyzed both hemocompatibility and immunoreactivity of these methacrylate-based HBPs ex vivo using primary human blood cell assays and image analyses following intravenous injection into mice. The results show that, regardless of charge, endotoxin-free HBPs had minimal effects on coagulation, platelet, complement, or T cell activation. However, high concentrations (100 μg mL) of cationic HBPs led to significant dendritic cell activation, suggesting the potential application of these nanoparticles as vaccine adjuvants to aid efficient antigen presentation. Biodistribution studies showed that intravenously administered charge-neutral HBPs had a longer retention time in the circulation than cationic or anionic HBPs; whereas these neutral HBPs were eventually cleared in the urine, charged HBPs mainly accumulated in liver and spleen. Overall, these results demonstrate that, regardless of surface charge, HBPs display a high level of hemocompatibility. In contrast, immunoreactivity and biodistribution are significantly influenced by charge. Manipulation of surface charge may thus be a useful method by which nanomaterials such as HBPs can be tailored to different clinical applications.
纳米医学的益处可能会受到将外源物质注入血液中所产生的血液相容性和免疫反应性问题的限制。为了了解表面电荷如何影响聚合物纳米颗粒与血液成分的相互作用，我们合成了三种尺寸相似、电荷不同的结构明确的超支化聚合物（HBPs），并通过原代人血细胞检测和静脉注射小鼠后的图像分析，在体外分析了这些基于甲基丙烯酸酯的HBPs的血液相容性和免疫反应性。结果表明，无论电荷如何，无内毒素的HBPs对凝血、血小板、补体或T细胞激活的影响最小。然而，高浓度（100μg/mL）的阳离子HBPs导致显著的树突状细胞激活，这表明这些纳米颗粒作为疫苗佐剂有助于有效抗原呈递的潜在应用。生物分布研究表明，静脉注射的电荷中性HBPs在循环中的保留时间比阳离子或阴离子HBPs长；而这些中性HBPs最终通过尿液清除，带电的HBPs主要积聚在肝脏和脾脏中。总体而言，这些结果表明，无论表面电荷如何，HBPs都具有高度的血液相容性。相比之下，免疫反应性和生物分布受电荷的显著影响。因此，操纵表面电荷可能是一种有用的方法，通过这种方法可以将HBPs等纳米材料定制用于不同的临床应用。
