Harmatys Kara M, Cole Erin L, Smith Bradley D
Department of Chemistry and Biochemistry, University of Notre Dame , 236 Nieuwland Science Hall, Notre Dame, 46556 Indiana, United States.
Mol Pharm. 2013 Nov 4;10(11):4263-71. doi: 10.1021/mp400357v. Epub 2013 Oct 22.
Deep-red fluorescent molecular probes are described that have a dendritic molecular architecture with a squaraine rotaxane core scaffold and multiple peripheral iminodiacetate groups as the bone targeting units. Iminodiacetates have an inherently lower bone affinity than bisphosphonates, and a major goal of the study was to determine how many appended iminodiacetate groups are required for effective deep-red fluorescence imaging of bone in living rodents. A series of in vitro and in vivo imaging studies showed that a tetra(iminodiacetate) probe stains bones much more strongly than an analogous bis(iminodiacetate) probe. In addition, a control tetra(iminodipropionate) probe exhibited no bone targeting ability. The tetra(iminodiacetate) probe targeted the same regions of high bone turnover as the near-infrared bisphosphonate probe OsteoSense750. Longitudinal studies showed that the fluorescence image signal from living mice treated with the tetra(iminodiacetate) probe was much more stable over 19 days than the signal from OsteoSense750. The narrow emission band of the tetra(iminodiacetate) probe makes it very attractive for inclusion in multiplex imaging protocols that employ a mixture of multiple fluorescent probes in preclinical studies of bone growth or in fluorescence guided surgery. The results also suggest that molecules or nanoparticles bearing multivalent iminodiacetate groups have promise as bone targeting agents with tunable properties for various pharmaceutical applications.
本文描述了一种深红色荧光分子探针，其具有以方酸轮烷为核心支架、多个外围亚氨基二乙酸基团作为骨靶向单元的树枝状分子结构。亚氨基二乙酸的骨亲和力本质上低于双膦酸盐，该研究的一个主要目标是确定在活体啮齿动物中进行有效的骨深红色荧光成像需要多少个附加的亚氨基二乙酸基团。一系列体外和体内成像研究表明，四（亚氨基二乙酸）探针比类似的双（亚氨基二乙酸）探针更强烈地染色骨骼。此外，对照四（亚氨基二丙酸）探针没有表现出骨靶向能力。四（亚氨基二乙酸）探针与近红外双膦酸盐探针OsteoSense750靶向相同的高骨转换区域。纵向研究表明，用四（亚氨基二乙酸）探针处理的活体小鼠的荧光图像信号在19天内比OsteoSense750的信号更稳定。四（亚氨基二乙酸）探针的窄发射带使其非常适合用于多重成像方案，该方案在骨生长的临床前研究或荧光引导手术中使用多种荧光探针的混合物。结果还表明，带有多价亚氨基二乙酸基团的分子或纳米颗粒有望作为具有可调节特性的骨靶向剂用于各种药物应用。
