Optimization and Synthesis of Perfluorocarbon Nanoemulsion with Fluorous Photosensitizer for Photodynamic Therapy

Perfluorocarbon-based nanoemulsions (PFC-NEs) have been shown to be an effective tool for oxygen delivery in various therapeutic modalities, including photodynamic therapy (PDT) in cancer treatment. PFC droplets are able to transport and supply oxygen to hypoxic cells as well as enhance the singlet oxygen generation by the photosensitizer (PS), functions which make them a promising platform for PDT. To further enhance PDT efficacy, we synthesized PFC-NEs with fluorous PS that is soluble in the perfluorocarbon phase, creating a closer proximity of the PS to the dissolved oxygen in PFC. However, the fluorous PS used in this work had a high tendency to leak into the aqueous phase with a surfactant, leading to less than desirable encapsulation efficiency (EE%). Therefore, the main goal of this study is to develop a formulation to ensure high EE% of fluorous PS in PFC droplets. PFC-NEs were prepared by ultrasonic emulsification and were characterized using dynamic light scattering, UV-Vis and fluorescence spectroscopy. The optimization of the PFC-NE formulation did not significantly affect the nanoemulsion properties, such as hydrodynamic diameter, polydispersity index and colloidal stability, and successfully increased EE%, as well as improved dark cytotoxicity profile and enhanced photoinduced cytotoxicity of PFC-NE.

The study was carried out using the equipment of the Core Facility “New Materials and Technologies” at the Emanuel Institute of Biochemical Physics, Russian Academy of Sciences.