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.
