Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA.
Biomaterials. 2011 Dec;32(35):9383-90. doi: 10.1016/j.biomaterials.2011.08.064. Epub 2011 Sep 3.
Medical implant-mediated inflammatory responses, often involving high levels of macrophages, are typically determined by histological analyses. These methods however are time consuming and require many animals to monitor the kinetics of inflammatory reactions and to generate reproducible outcomes. Recent studies have shown that activated macrophages in inflamed tissue express high levels of folate receptor (FR). In this study, FR-targeting NIR nanoprobes were fabricated and then tested for their ability to detect and quantify the extent of biomaterial-mediated inflammatory responses in vivo. Indeed, FR-targeting nanoprobes preferentially accumulate on activated macrophage surfaces. When administered intravenously, we found that the FR-targeting nanoprobes distinctively gathered in the inflamed tissues and that a different extent of FR-targeting nanoprobe gathering could be found in tissues implanted with different types of biomaterials. Most importantly, we found that there was a good relationship between the extent of inflammatory reactions and the intensity of nanoprobe-associated NIR signal in tissue. Our results support that FR-targeting NIR nanoprobes can be used to monitor and quantify the extent of macrophage recruitment and the degree of an implants' biocompatibility in real time.
医学植入物介导的炎症反应，通常涉及高水平的巨噬细胞，通常通过组织学分析来确定。然而，这些方法耗时且需要大量动物来监测炎症反应的动力学，并产生可重复的结果。最近的研究表明，炎症组织中活化的巨噬细胞表达高水平的叶酸受体（FR）。在这项研究中，制备了靶向 FR 的近红外纳米探针，并测试了它们在体内检测和定量生物材料介导的炎症反应程度的能力。事实上，靶向 FR 的纳米探针优先聚集在活化的巨噬细胞表面。当静脉内给药时，我们发现靶向 FR 的纳米探针明显聚集在炎症组织中，并且在植入不同类型生物材料的组织中可以发现不同程度的靶向 FR 的纳米探针聚集。最重要的是，我们发现炎症反应的程度与组织中与纳米探针相关的近红外信号强度之间存在良好的关系。我们的结果支持靶向 FR 的近红外纳米探针可用于实时监测和定量巨噬细胞募集的程度以及植入物的生物相容性程度。
