Pham Christine T N, Thomas Dennis G, Beiser Julia, Mitchell Lynne M, Huang Jennifer L, Senpan Angana, Hu Grace, Gordon Mae, Baker Nathan A, Pan Dipanjan, Lanza Gregory M, Hourcade Dennis E
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Knowledge, Discovery and Informatics, Pacific Northwest National Laboratory, Richland, WA, USA.
Nanomedicine. 2014 Apr;10(3):651-60. doi: 10.1016/j.nano.2013.10.012. Epub 2013 Nov 8.
Nanoparticles offer new options for medical diagnosis and therapeutics with their capacity to specifically target cells and tissues with imaging agents and/or drug payloads. The unique physical aspects of nanoparticles present new challenges for this promising technology. Studies indicate that nanoparticles often elicit moderate to severe complement activation. Using human in vitro assays that corroborated the mouse in vivo results we previously presented mechanistic studies that define the pathway and key components involved in modulating complement interactions with several gadolinium-functionalized perfluorocarbon nanoparticles (PFOB). Here we employ a modified in vitro hemolysis-based assay developed in conjunction with the mouse in vivo model to broaden our analysis to include PFOBs of varying size, charge and surface chemistry and examine the variations in nanoparticle-mediated complement activity between individuals. This approach may provide the tools for an in-depth structure-activity relationship study that will guide the eventual development of biocompatible nanoparticles.
Unique physical aspects of nanoparticles may lead to moderate to severe complement activation in vivo, which represents a challenge to clinical applicability. In order to guide the eventual development of biocompatible nanoparticles, this team of authors report a modified in vitro hemolysis-based assay developed in conjunction with their previously presented mouse model to enable in-depth structure-activity relationship studies.
纳米颗粒能够通过成像剂和/或药物载荷特异性靶向细胞和组织,为医学诊断和治疗提供了新的选择。纳米颗粒独特的物理特性给这项前景广阔的技术带来了新的挑战。研究表明,纳米颗粒常常引发中度至重度的补体激活。我们利用人体体外试验证实了之前在小鼠体内的实验结果,并开展了机理研究,确定了几种钆功能化全氟碳纳米颗粒(PFOB)与补体相互作用的调控途径和关键成分。在此,我们采用一种与小鼠体内模型相结合开发的改良体外溶血试验,扩大分析范围,纳入不同大小、电荷和表面化学性质的PFOB,并研究个体之间纳米颗粒介导的补体活性差异。这种方法可能为深入的构效关系研究提供工具,从而指导生物相容性纳米颗粒的最终研发。
纳米颗粒独特的物理特性可能导致体内中度至重度的补体激活,这对临床应用构成了挑战。为了指导生物相容性纳米颗粒的最终研发,该作者团队报告了一种与他们之前提出的小鼠模型相结合开发的改良体外溶血试验,以实现深入的构效关系研究。