Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Biomaterials. 2011 Oct;32(30):7651-61. doi: 10.1016/j.biomaterials.2011.06.030. Epub 2011 Jul 23.
Dysregulated host inflammatory response causes many diseases, including cardiovascular and neurodegenerative diseases, cancer, and sepsis. Sensitive detection of the site of inflammation will, therefore, produce a wide-ranging impact on disease diagnosis and treatment. We hypothesized that nanoprobes designed to mimic the molecular interactions occurring between inflamed leukocytes and endothelium may possess selectivity toward diverse host inflammatory responses. To incorporate inflammation-sensitive molecular interactions, super paramagnetic iron oxide nanoparticles were conjugated with integrin lymphocyte function-associated antigen (LFA)-1 I domain, engineered to mimic activated leukocytes in physiology. Whole body optical and magnetic resonance imaging in vivo revealed that leukocyte-mimetic nanoparticles localized preferentially to the vasculature within and in the invasive front of the tumor, as well as to the site of acute inflammation. This study explored in vivo detection of tumor-associated vasculature with systemically injected inflammation-specific nanoparticles, presenting a possibility of tumor detection by inflamed tumor microenvironment.
失调的宿主炎症反应可导致多种疾病,包括心血管疾病和神经退行性疾病、癌症和败血症。因此,对炎症部位的敏感检测将对疾病的诊断和治疗产生广泛的影响。我们假设,设计用于模拟炎症白细胞和内皮细胞之间发生的分子相互作用的纳米探针可能对不同的宿主炎症反应具有选择性。为了纳入炎症敏感的分子相互作用,超顺磁性氧化铁纳米颗粒与整合素淋巴细胞功能相关抗原(LFA)-1 I 结构域缀合,该结构域经过工程设计可模拟生理状态下的激活白细胞。体内的全身光学和磁共振成像显示,类白细胞纳米颗粒优先定位于肿瘤内部和侵袭前沿的脉管系统,以及急性炎症部位。这项研究探索了用系统注射的炎症特异性纳米颗粒对肿瘤相关血管的体内检测,为通过炎症肿瘤微环境检测肿瘤提供了可能性。