NMR spectroscopy in Biomedicine and Materials Science: A Focus on Biocompatible Hyperpolarized 29Si MRI Imaging Probes and Polymer Composites

Abstract

NMR spectroscopy in Biomedicine and Materials Science: A Focus on Biocompatible Hyperpolarized 29Si MRI Imaging Probes and Polymer Composites Jiwon Kim Department of Bionano Technology The Graduate School Hanyang University This dissertation spans two pivotal areas of study: the development of 29Si hyperpolarized silicon and silica-based MRI imaging probes, and the pre-screening of biodegradability for microcapsules. Within the realm of Dynamic Nuclear Polarization (DNP), this research probes the intricate effects on hyperpolarization from variables such as particle size, intraparticle environment, interfacial dynamics with solvents, and the extent of isotope substitution. The 29Si isotope plays a key role in our investigation, serving to fine-tune high-resolution MRI imaging probes. We utilized a fully 29Si-enriched tetraethyl orthosilicate (TEOS) precursor to synthesize silicon nanoparticles (Si NPs) with varying degrees of enrichment, which displayed significant hyperpolarization. These particles exhibited enhanced signal properties following DNP polarization, which is in line with our goal to enhance silicon- based MRI for precise biomedical imaging. Building on previous conclusions, we have synthesized 29Si-enriched silicon NPs with precision, manipulating their physicochemical characteristics. Varying the enrichment to 10% and 15%, we mapped their hyperpolarization across various states, from solid at cryogenic temperatures to depolarization at ambient conditions. These particles achieved polarization via DNP, yielding signal enhancements that exceeded expectations from isotope enrichment alone, suggesting an effective mechanism of surface polarization and spin diffusion to the core. Furthermore, we perfected the synthesis of selectively 29Si-enriched SiO2 NPs, affording us fine control over their size, morphology, and internal structure. Our data indicated that higher shell enrichments of 29Si lead to larger signal amplifications, highlighting the impact of shell enrichment on overall polarization, irrespective of the core's high isotopic concentration. The production of shell-enriched samples paves the way for bioinspired SiO2 NPs to become sophisticated MRI probes, with DNP-NMR facilitating rapid surface composition characterization and a deeper understanding of biochemical interactions. This research aims to profoundly impact the field of diagnostic imaging by offering a swift method for assessing NP surface chemistry. Advancements in NP design and our comprehension of hyperpolarization mechanisms are poised to propel silicon MRI into a non-invasive, highly targeted imaging technique. Additionally, the potential of these NPs as drug delivery systems promises a novel paradigm in personalized medicine through a theragnostic approach. Now, shifting the focus, this section aims to explore the study of biodegradability of microcapsules using NMR. The following chapters discuss biodegradability assessment techniques designed for professionals in various industries. It is important to note that DNP technology was not employed; instead, conventional 1H-NMR spectroscopy was applied. In chapter 4.1, we present an innovative synthesis and biodegradation assessment methodology for eco-friendly microcapsules crafted from natural polymer blends. Amid increasing ecological concerns regarding microplastics, the necessity to evaluate the biodegradability of eco-friendly polymer composites has become crucial. Advanced analytical techniques were employed to scrutinize the initial biodegradation stages of these microcapsules, unveiling insights into their enzymatic degradation routes. Particularly, microcapsules containing Hydroxyethyl cellulose (HEC) exhibited rapid biodegradability when subjected to enzymatic action. The proposed use of liquid 1H-NMR spectroscopy to monitor temporal linewidth variations offers an efficient, lab-scale biodegradability assessment method. This technique is anticipated to become a universal tool for evaluating the biodegradability of diverse microcapsules. Advancing this theme, Chapter 4.2 details specific biodegradation mechanisms of the developed microcapsules. We describe the synthesis and characterization of biodegradable microcapsules via the complex coacervation technique, achieving a consistent size distribution. Utilizing 1H-NMR spectroscopy, the enzymatic degradation process induced by alginate lyase was investigated. The microcapsules, comprised of gelatin, alginate, and glutaraldehyde, maintained stable morphological and chemical structures. The enzymatic breakdown of alginate was verified by 1H-NMR, manifesting as distinct signal changes indicative of biodegradation. This study provides a profound understanding of biodegradation pathways, facilitated by targeted enzyme specificity, and introduces a promising avenue for modulating microcapsule degradation rates, beneficial for both industrial and pharmaceutical applications. Ultimately, the DNP studies and biodegradability pre-screening methods converge to highlight the versatility and indispensability of NMR spectroscopy as a quintessential analytical instrument. It is the cohesive element that links these distinct yet interrelated fields of study. NMR spectroscopy not only yields high-resolution insights but also fosters a holistic view that synergizes advanced imaging techniques with systematic material behavior assessments. The synergy of these investigations reaffirms the transformative potential of NMR spectroscopy in spearheading novel solutions to a spectrum of scientific endeavors.