Multifunctional Nanodiamond Platforms for Targeted Imaging and Therapy

用于靶向成像和治疗的多功能纳米金刚石平台

• 批准号: 1343991
• 负责人: Dean Ho
• 金额: $ 31.36万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-11 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1343991&HistoricalAwards=false
• 关键词: Multifunctional; Nanodiamond; Platforms; Targeted; Imaging

This award by the Biomaterials program in the Division of Materials Research to Northwestern University is to study the interactions of nanodiamond (ND)-gadolinium III (Gd(III)) conjugates, and to further optimize the relaxivity and integration with polyethylenimine (PEI) for enhanced imaging and medical treatments. The development of novel imaging and therapeutic modalities with significantly enhanced performance over current standards remains an important focus at the intersection of biomaterials and nanoengineering. Nanodiamonds serve as promising biomaterial platforms as they unite a spectrum of unique chemical/physical properties, enabling significantly improved capabilities in imaging and therapy. Recent studies have shown that ND-gadolinium (III) complexes can produce a 12-fold enhancement in per-Gd relaxivity, yielding among the highest values that have been reported. Furthermore, gene therapy challenges are often based on the inability to develop platforms that integrate both safety and efficacy. We have shown that complexes comprised of NDs and the polyethylenimine polymer yield a 70-fold enhancement in DNA transfection efficacy. Furthermore, both the ND-Gd(III) and ND-PEI hybrid complexes are biocompatible. This project will modulate the linker length between ND surfaces and Gd(III) to optimize relaxivity. The ND-Gd(III) complexes will then be combined with PEI and a targeting agent to generate order of magnitude increases in both imaging and therapy into a single platform. Optimized by fundamental science and engineering investigations, this nanodiamond platform will combine unprecedented improvements to contrast and therapeutic efficacy in targeted drug delivery and imaging. These advancements will further serve as the foundation for developing new educational modules and hands-on research experiences for K-12 students. The planned preparation of ND block and magnetic resonance imaging kits to educate students is expected to provide the interesting nature of ND facets/electrostatics and how these materials could mediate drug binding/release and imaging. In addition to their research training in science and engineering, the graduate students supported by this proposal will also serve as mentors for undergraduate researchers as well as K-12 students and high school teachers from partnering institutions who are taking part in the learning modules prepared. The integration of scientific discoveries and educational resources from this project will thus serve as a foundation for the education and training of the scientific and engineering leaders of tomorrow.Current challenges in understanding, diagnosing, and treating cancer are based on the needs of improved imaging and therapy. To address these challenges, the investigators are developing a nanodiamond-based platform that is capable of mediating greater than 10-fold increases in imaging and drug treatment efficiency, which are significant improvements over current standards. The integration of fundamental studies with applied engineering will be used to synthesize integrated nanodiamond complexes to target, image, and treat a selected breast cancer model, with the ultimate goal of optimizing diagnostic capabilities and therapeutic efficiency while remaining biocompatible and safe. It is envisioned that this novel technology will provide unprecedented advances in imaging/diagnostics and cancer therapy, among other areas. The discoveries realized from this study will also inspire new methodologies for educating and training the next generation of science and engineering leaders. To merge scientific discovery with educational impact, the investigators are planning to develop innovative experimental modules using imaging kits and nanodiamond blocks that could be used to educate students from K-12. Furthermore, these kits will be used as a hands-on tool for magnetic resonance imaging instruction. Graduate students supported by this study will serve as educational module leaders to instruct partnering K-12 teachers on the emerging applications of nanodiamonds, as well as the use of these kits. Furthermore, these graduate students will mentor undergraduate students in designated research projects, and these activities are expected to provide an optimal framework for scientific impact and educationally developing the next generation of scientific leadership.

生物材料计划在西北大学材料研究部的奖项是为了研究纳米座（ND） - gadolinium III（GD（III））结合物的相互作用，并进一步优化了与聚乙基苯胺（PEI）的放松性和整合，以增强成像和药物治疗。与当前标准相比，具有显着增强性能的新型成像和治疗方式的发展仍然是生物材料和纳米工程的交集的重要重点。纳米原子座是有前途的生物材料平台，因为它们结合了一系列独特的化学/物理特性，从而可以显着提高成像和治疗的能力。最近的研究表明，ND-GADOLIUM（III）复合物可以在每GD宽松度中产生12倍增强的增强，从而在已报道的最高值中产生。此外，基因治疗挑战通常是基于无法开发整合安全性和功效的平台。我们已经表明，由NDS组成的复合物和聚乙烯亚胺聚合物在DNA转染疗效中产生70倍。此外，ND-GD（III）和ND-PEI杂交复合物都是生物相容性的。该项目将调节ND表面和GD（III）之间的接头长度，以优化松弛性。然后，ND-GD（III）复合物将与PEI和靶向剂结合使用，以使成像和治疗的数量级增加到一个平台中。该纳米原子平台通过基本科学和工程调查进行了优化，将结合前所未有的改进，以在靶向药物输送和成像中进行对比和治疗功效。这些进步将进一步为K-12学生开发新的教育模块和动手研究经验的基础。预计ND块和磁共振成像套件的计划制备预计将提供ND方面/静电的有趣性质，以及这些材料如何介导药物结合/释放和成像。除了在科学和工程学方面的研究培训外，得到该建议的支持的研究生还将担任本科研究人员以及K-12的学生和高中老师的导师，这些学生来自与他们一起参加学习模块的合作机构。因此，该项目的科学发现和教育资源的融合将成为明天的科学和工程领导者的教育和培训的基础。理解，诊断和治疗癌症方面的挑战基于改进的成像和治疗的需求。为了应对这些挑战，研究人员正在开发一个基于纳米原子的平台，该平台能够介导成像和药物治疗效率的10倍以上，这比当前标准相比有了显着改善。基本研究与应用工程的整合将用于合成综合的纳米座复合体以靶向，图像和治疗所选的乳腺癌模型，其最终目标是优化诊断能力和治疗效率，同时保持生物相容性和安全。可以预见的是，这项新型技术将在成像/诊断和癌症治疗等方面提供前所未有的进步。从这项研究中实现的发现还将激发教育和培训下一代科学和工程领导者的新方法。为了将科学发现与教育影响合并，研究人员计划使用成像套件和纳米座块开发创新的实验模块，这些模块可用于教育K-12的学生。此外，这些套件将用作磁共振成像教学的动手工具。这项研究支持的研究生将担任教育模块领导者，以指导K-12老师伙伴有关纳米登蒙蒙德的新兴应用以及这些套件的使用。此外，这些研究生将指导指定研究项目的本科生，并且这些活动有望为科学影响提供最佳框架，并在教育上发展下一代科学领导力。