Hultman Kristi L, Raffo Anthony J, Grzenda Adrienne L, Harris Paul E, Brown Truman R, O'Brien Stephen
Department of Applied Physics, Columbia University, 200 SW Mudd Building, New York, New York 10027, USA.
ACS Nano. 2008 Mar;2(3):477-84. doi: 10.1021/nn700400h.
We demonstrate the development and successful application of immunotargeted superparamagnetic iron oxide nanoparticles (ITSIONs), with in vivo magnetic resonance diagnostic and potential drug delivery capability for kidney disease. Further, the versatility of the conjugation chemistry presents an attractive route to the preparation of a range of biomolecule-nanoparticle conjugates. The ITSION contrast agent is a stable, biocompatible, targeted nanoparticle complex that combines a monodisperse iron oxide nanoparticle core with a functionalized phospholipid coating conjugated to antibodies that is capable of targeting normal cells expressing specific target antigens. The plasma half-life and R1 and R2 relaxivities suggest sufficient time for targeted binding while clearing from the system quick enough for detection of specific contrast enhancement. RT1 anti-MHC Class II antibodies were used to target the renal medulla of the rat, a section of the kidney in which MHC Class II, associated with inflammation, is specifically expressed. For in vivo resonance imaging, we compare phospholipid coated nanoparticles, nonspecific ITSIONs, and RT1 ITSIONs. Enhanced binding of the RT1 ITSIONS indicates specificity for the renal medulla and thus potential for disease detection or drug delivery.
我们展示了免疫靶向超顺磁性氧化铁纳米颗粒（ITSIONs）的开发及其成功应用，该纳米颗粒具有用于肾脏疾病的体内磁共振诊断和潜在的药物递送能力。此外，共轭化学的多功能性为制备一系列生物分子-纳米颗粒共轭物提供了一条有吸引力的途径。ITSION造影剂是一种稳定、生物相容的靶向纳米颗粒复合物，它将单分散的氧化铁纳米颗粒核心与功能化磷脂涂层结合，该涂层与能够靶向表达特定靶抗原的正常细胞的抗体共轭。血浆半衰期以及R1和R2弛豫率表明有足够的时间进行靶向结合，同时从系统中清除得足够快，以便检测到特异性对比增强。使用RT1抗MHC II类抗体靶向大鼠的肾髓质，肾髓质是肾脏的一部分，其中与炎症相关的MHC II类特异性表达。对于体内共振成像，我们比较了磷脂包被的纳米颗粒、非特异性ITSIONs和RT1 ITSIONs。RT1 ITSIONS的增强结合表明对肾髓质具有特异性，因此具有疾病检测或药物递送的潜力。
