STTR Phase I: Non-Toxic Nanoparticles for BRET-Based Molecular Imaging

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。这个小企业技术转让（STTR）第一阶段项目将导致无毒的多模态纳米粒子为基础的分子探针在体内成像的示范。第一阶段项目的目标是展示发光硫化铋纳米颗粒的合成和涂层，其在近红外（NIR）发射，用作多模态探针。这些探针可以通过NIR荧光发射检测或作为自发光探针通过生物发光共振能量转移到发光纳米晶体（BRET-LN）检测。此外，硫化铋可用作基于X射线的成像的造影剂。在大多数近红外发射纳米颗粒中存在有毒金属，如Cd，As，In和Hg，并且相对缺乏详细的安全数据，这为人类使用建立了一个重要的安全屏障。硫化铋是一种潜在的无毒生物成像材料。铋化合物在药物制剂中用于治疗腹泻、梅毒和消化性溃疡等疾病已有超过世纪的历史。在美国，每年约有500吨铋用于化学、化妆品和医疗产品中，直接用于人类。这项研究的更广泛的影响是开发一种灵敏的多功能分子成像探针，用于医学成像和手术间染色程序。新的探头最终将提供一种更有效的手段，以光学方式对人类疾病进行成像，从而规避其他光学成像技术固有的成像深度和信噪比限制。这种能力将转化为重要应用的发展，如早期癌症检测。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This Small Business Technology Transfer (STTR) Phase I project will result in the demonstration of non-toxic multi-modality nanoparticle-based molecular probes for in vivo imaging. The objective of the Phase I project is to demonstrate the synthesis and coating of luminescent bismuth sulfide nanoparticles emitting in the near infrared (NIR) for use as multi-modality probes. These probes may be detected by NIR fluorescence emission or as self-illuminated probes through Bioluminescence Resonance Energy Transfer to Luminescent Nanocrystals (BRET-LN). Moreover, bismuth sulfide can be used as a contrast agent for X-ray-based imaging. The presence of toxic metals such as Cd, As, In and Hg in most of the NIR emissive nanoparticles and the relative lack of detailed safety data establish a significant safety barrier for use in humans. Bismuth sulfide is a potentially non-toxic material for bioimaging. Bismuth compounds have been used in pharmaceutical formulations for more than a century to treat maladies such as diarrhea, syphilis, and peptic ulcers. In the U.S., approximately 500 tons of bismuth are used in chemical, cosmetic, and medical products with direct human experience each year. The broader impacts of this research are the development of a sensitive multi-functional molecular imaging probe for use in medical imaging and inter-operative staining procedures. The new probe will ultimately provide a more efficient means to image disease in humans optically, circumventing inherent imaging depth and signal-to-noise limitations of other optical imaging technologies. This capability will translate to the development of important applications such as early cancer detection.