Multifunctional Nanodiamond Platforms for Targeted Imaging and Therapy

这一奖项由西北大学材料研究部生物材料计划颁发，旨在研究纳米金刚石(ND)-Gd(III)结合物的相互作用，并进一步优化松弛性能和与聚乙烯亚胺(PEI)的集成，以增强成像和医疗治疗。在生物材料和纳米工程的交叉点上，显著提高性能的新型成像和治疗模式的开发仍然是生物材料和纳米工程的重要焦点。纳米钻石是一种很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/物理性质，使成像和治疗能力得到显著改善。最近的研究表明，Nd-Gd(III)配合物可以产生12倍的Per-Gd驰豫，产生已报道的最高值之一。此外，基因治疗的挑战往往基于无法开发出集安全性和有效性于一体的平台。我们已经证明，由NDS和聚乙烯亚胺聚合物组成的复合体在DNA转染率方面提高了70倍。此外，NdGd(III)和NdPEI杂化配合物都具有良好的生物相容性。这个项目将通过调节Nd表面和Gd(III)之间的连接基长度来优化弛豫度。然后，ND-Gd(III)络合物将与PEI和靶向剂结合，在单一平台上产生成像和治疗的数量级增长。经过基础科学和工程研究的优化，这个纳米钻石平台将在靶向药物输送和成像方面结合对比度和治疗效果的前所未有的改进。这些进展将进一步成为为K-12学生开发新的教育模块和实践研究体验的基础。为了教育学生，计划准备ND块和磁共振成像试剂盒，预计将提供ND小面/静电学的有趣性质，以及这些材料如何介导药物结合/释放和成像。除了他们在科学和工程方面的研究培训外，这项建议支持的研究生还将担任本科生研究人员以及来自合作机构的K-12学生和高中教师的导师，他们参加了准备好的学习模块。因此，该项目的科学发现和教育资源的整合将为未来科学和工程领导者的教育和培训奠定基础。目前在认识、诊断和治疗癌症方面的挑战是基于改进成像和治疗的需要。为了应对这些挑战，研究人员正在开发一种基于纳米钻石的平台，该平台能够使成像和药物治疗效率提高10倍以上，这是对当前标准的重大改进。基础研究与应用工程的结合将被用于合成集成的纳米钻石复合体，以靶向、成像和治疗选定的乳腺癌模型，最终目标是在保持生物兼容性和安全性的同时优化诊断能力和治疗效率。可以预见，这项新技术将在成像/诊断和癌症治疗等领域提供前所未有的进步。这项研究的发现也将启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结合起来，研究人员计划开发创新的实验模块，使用成像工具包和纳米钻石块，可以用来教育从K-12岁的学生。此外，这些试剂盒将被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负责人，就纳米钻石的新兴应用以及这些工具包的使用向合作的K-12教师提供指导。此外，这些研究生将在指定的研究项目中指导本科生，这些活动预计将为科学影响和教育培养下一代科学领导力提供最佳框架。

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.