Choi Hak Soo, Liu Wenhao, Misra Preeti, Tanaka Eiichi, Zimmer John P, Itty Ipe Binil, Bawendi Moungi G, Frangioni John V
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, Massachusetts 02215, USA.
Nat Biotechnol. 2007 Oct;25(10):1165-70. doi: 10.1038/nbt1340. Epub 2007 Sep 23.
The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.
纳米技术领域在人类疾病的诊断和治疗方面具有巨大潜力。然而,大多数纳米颗粒的大小和电荷使其难以作为完整的纳米颗粒从体内有效清除。如果没有这种清除或它们生物降解为生物良性成分,毒性可能会增强,放射成像也会受到阻碍。以啮齿动物静脉注射量子点作为模型系统,我们精确确定了无机含金属纳米颗粒肾脏过滤和尿液排泄的要求。两性离子或中性有机涂层可防止血清蛋白吸附,否则血清蛋白会使流体动力学直径增加超过15纳米并阻碍肾脏排泄。最终流体动力学直径小于5.5纳米会导致量子点快速有效地经尿液排泄并从体内清除。这项研究为生物医学应用中生物靶向纳米颗粒的设计和开发奠定了基础。