Development of Noninvasive Oxygen Imaging Approach Using Water-dispersible Microparticulate Lithium Naphtalocyanine Probes

Marissa Gibides* and Andrey Bobko

Cancer Institute, West Virginia University, Morgantown, WV 26505

Presentation Category: Oral-Science & Technology (Oral Presentation #19)

Student’s Major: Neuroscience

Introduction: Blood flow associated with tumor vasculature is often irregular, sluggish, and intermittent. This results in areas of hypoxia, which is a common feature of new, abnormal growth. It is known that the presence of these hypoxic cells leads to therapeutic resistance in preclinical tumors as well as harming the ability to control human malignancies. In this study, we developed a noninvasive oxygen imaging approach using a water-dispersible micro particulate LiNc-BuO probe. Results: Lithium naphtalocyanine probes (LiNc-BuO) were prepared using microfluidics techniques which generate uniform microparticles with a diameter in the range 5-20 µm dispersible in the water solution. Microparticles were coated with different coating: cell-adhesive polydopamine, native to tissue microenvironment hyaluronic acid, and just bare lithium naphtalocyanine surface. In vivo experiments of microparticles biocompatibility and distribution in tumor tissue were performed using an orthotopic model of mammary tumor in mice. PyMT tumor cells (0.5 million) and microcrystal probe (0.5 mg) in 50 uL media were injected into the mammary fat pad. Tumors were growing, measured, and imaged once a week till tumor size reached 1 cm. Tumors were collected, fixed cross-sectioned, and analyzed on the density of the particles in each layer. Tumors were then stained for the hypoxic areas. Conclusion: Microfluidic technics allow for the production of uniformly distributed microparticles of various sizes. The coating of LiNc-BuO particles with biocompatible polymers (polydopamine and hyaluronic acid) significantly improves microparticles' biocompatibility and tissue distribution. The developed approach allows for fast and accurate oxygen imaging in a preclinical tumor mouse model.

Funding: NIH

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course