RUI: Exploring Mechanisms of Immunomodulation of Functionalized Cellulose Nanomaterial: A Comprehensive Interdisciplinary Approach

Non-technical abstract:

Cellulose nanocrystals (CNCs) are tiny materials made from cellulose; a natural substance easily found in plants. These CNCs have shown promise in various applications, including in medicine and drug development. CNCs are already used in pharmaceuticals, however their potential in other medical areas, such as supporters of the immune responses and serving as components in vaccines, has not been fully explored.

Our research aims to investigate how CNCs can improve the immune system by studying in what manner their shapes and sizes can influence their actions within the cells. We have found that CNCs modified with certain positive-charged polymers do not harm cells, but they can trigger beneficial immune responses. To further understand these effects, we add fluorescent tags to the positive-charged CNCs to track how they are taken up by cells and how they interact with different parts of the cell and improve our immune system.

This research is important because it will provide new insights into how CNCs improve the immune system and how their characteristics influence this process. The findings could lead to the development of new, sustainable materials for medical applications, particularly in enhancing immune responses. Additionally, this research project enhances research opportunities at SUNY Plattsburgh, particularly for underrepresented and first-generation college students in science, technology, engineering, and math (STEM) fields.

Working in this project, students gain hands-on research experience and receive mentorship from experienced professors, making them more competitive for advanced studies and careers in biomedical sciences and nanotechnology. Finally, the professors and students working in this project share their findings with the broader community through talks on nanotechnology and sustainable biomaterials, aiming to advance the national health and increase scientific literacy and interest in science among high school students, teachers and community at large.

Technical abstract:

Cellulose nanocrystals (CNCs) are renewable, cellulose-based biomaterials with diverse applications, including potential use in biomedicine. While CNCs have been employed in the pharmaceutical industry, their capabilities as immunomodulators and vaccine adjuvants are not fully explored. This proposal aims to investigate the immunological responses elicited by CNCs, focusing on the mechanisms and physicochemical characteristics that influence these responses.

Our preliminary studies have shown that CNCs functionalized with cationic polymers like poly(2-methacryloylethyl)trimethylammonium chloride (METAC) induce appropriate immune responses without cytotoxicity. In this study we further functionalize METAC-CNCs with fluorescent tags to study cellular uptake and organelle interactions. After functionalization of these cationic cellulose-based biomaterials, we assess their physicochemical properties, cytotoxicity and immunogenicity.

Then we analyze cellular intake and organelle interaction mitochondrial redox changes and lysosomal disruption. Finally, we correlate the physicochemical properties with their mechanisms of immunomodulation. The overarching significance of this research lies in 1) providing new insights into the immunogenicity and molecular mechanisms of CNCs; 2) shining a light on the relationship between CNCs' physicochemical properties, cellular localization, and immunomodulatory mechanisms, and 3) laying the groundwork for future in vivo studies to develop CNC-based biomaterials as immunomodulators.

This interdisciplinary project enhances the research environment at SUNY Plattsburgh, a primarily undergraduate institution (PUI), by creating nanotechnology-based research opportunities for underrepresented and first-generation students in STEM as well as improving publication records for both faculty and students. Finally, to engage the broader community, the PIs and students share their findings on nanotechnology and sustainable biomaterials to the public, including high school students and teachers, to promote scientific literacy and access to science and technology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.