IR-780 iodide, a near-infrared (NIR) fluorescent heptamethine dye, has attracted wide attention in the biomedical community. However, hydrophobicity and toxicity severely limit its further biomedical application. Although many successful efforts have been made to increase its solubility and biocompatibility, a strong fluorescent signal and longer retention time are in high demand in biomedical application in vivo as well as basic science research. In this work, we report the development of novel silica cross-linked micellar core–shell nanoparticles encapsulating IR-780 (NIR-Silica NPs) and their utility for biomedical imaging in vivo. Compared to free IR-780, the solubility of NIR-Silica NPs was not only greatly increased, but there was also a dramatic 5–7-fold enhancement of fluorescence intensity. More importantly, the exceptionally small size (25 nm) and colloidal stability of the NPs are also sufficient to realize the enhanced permeability and retention effect. In vitro cell viability assays further indicated that the NIR-Silica NPs are safer even at the highest concentration tested of 1.0 mg/mL. Finally, sentinel lymph node mapping and long-term tumor imaging in vivo demonstrated that the NIR-Silica NPs have a long circulation time and higher signal-to-noise ratio at a very low dye concentration and short exposure time (0.2 s). Therefore, the NIR-Silica NPs may be a promising fluorescence imaging agent for clinical application.
Keywords: Near-Infrared; Heptamethine Dye; Cross-Linked; Silica; Fluorescence; Optical Imaging.