Multi-emissive Boron PLA Nanoparticles for Vascular Optical Hypoxia Imaging

Cassandra L. Fraser

Department of Chemistry, College of Arts & Sciences, UVa

Richard J. Price

Department of Biomedical Engineering, UVa

Oxygen is vital to most forms of life and regulation of its concentration and reactivity in tissues is critical to good health. Many diseases are characterized by low levels of oxygen, hypoxia, which can compromise cell function and lead to tissue damage and death. These include cardiovascular diseases, stroke, cancer, diabetes and many more. Ischemia also plays a role in organ transplantation. Real-time measurement of O₂ levels in cells and tissues and correlation with biological processes would increase understanding of normal and pathological states, however reliable oxygen measurements can be difficult. Common electrode, histochemical and phosphorescence quenching methods are subject to spatial and temporal limitations and technical challenges. Recently the Fraser lab prepared a new boron biomaterial with rare multi-emissive properties. The presence of both intense fluorescence and oxygen sensitive phosphorescence in a single component, readily processable biomaterial shows great promise for ratiometric oxygen sensing. This combined with biocompatibility, easy synthesis and properties tuning, and high sensitivity, offers advantages over existing heavy metal dyes, particularly for hypoxia imaging. Recently Fraser and Price established a collaboration to investigate the potential of boron nanoparticles (BNPs) for optical imaging and real-time O₂ sensing in the microvasculature, with the goal of understanding the role that tissue PO₂ may play in driving collateral growth following occlusion. Appropriate microscope filters were procured and preliminary ex vivo and in vivo experiments were performed, demonstrating that BNP fluorescence is very bright, stable to photobleaching, and thus, suitable for tissue and in vivo imaging in gracilis adductor and cremaster muscle models. Next, in the proposed research, we must take advantage of BNP phosphorescence to quantify O₂ levels and image hypoxia following vascular blockage (Phase 1). Materials properties, e.g. emission wavelengths and oxygen sensitivities, will be modified through chemical synthesis to optimize imaging and O₂ sensing in tissues of interest (Phase 2). Finally, we will generate boron nanoparticles with targeting groups, namely antibodies to CD36, to increase the concentration and better localize the boron imaging and sensing agent in the microvasculature (Phase 3). This new research program enjoys considerable synergy with other collaborations at UVA and other institutions in cell trafficking, cancer and diabetes/islet cell transplant areas, along with industrial partnerships and intellectual property ventures. Progress toward these goals will constitute important advances in science and technology and make us highly competitive for outside funding.