Real time monitoring of biomaterial-mediated inflammatory responses via macrophage-targeting NIR nanoprobes

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. (C) 2011 Elsevier Ltd. All rights reserved.