Suppressing inflammation from inside out with novel NIR visible perfluorocarbon nanotheranostics

摘要

Highly innovative multimodal perfluorocarbon (PFC) nanoemulsions are presented. They serve simultaneously as dual-mode imaging reagents (NIR and ~(19)F MRI), and drug delivery vehicles for water insoluble cyclooxgenase-2 (COX-2) inhibitors. These features qualify them as theranostic. Cancer progression and metastasis are highly influenced by tumor microenvironment and inflammation. Infiltration of primary tumors with inflammation-promoting cells (e.g. macrophages) is a negative prognostic factor for cancer patient survival. We postulate that the suppression of COX-2 enzyme in macrophages by theranostic PFC nanoemulsions will result in changes in macrophage levels of accumulation in tumors and/or their phenotype, which can suppress tumor-promoting activity. The presented theranostic nanoemulsions are designed to label immune cells such as macrophages, and deliver celecoxib, a COX-2 inhibitor. The designed theranostic incorporates two fluorescent reporters: a near-infrared (NIR) fluorescent dye for improved optical in vivo imaging, and a distinct fluorescent dye for histological analysis of excised tissues. A high content of PFC in the theranostic allows ~(19)F MRI to quantitatively assess the distribution of the injected nanomedicine in the peritumoral area, and measure tumor-associated inflammation, while ~1H MRI provides anatomical context. NIR imaging is used as a complementary in vivo technique to assess biodistribution of the theranostic. We report preparation and characterization of the nanoemulsions' colloidal and optical stability, in vitro toxicity, and imaging capabilities. This theranostic offers flexibility for in vitro and in vivo inflammation imaging and histological analysis using three different imaging functionalities (fluorescence, NIR and ~(19)F MRI), advancing the monitoring and modulating of tumor-infiltrating immune cells in vivo.