Facile Synthesis of Lipid-Perfluorocarbon Nanoemulsion Coated with Silica Shell as an Ultrasound Imaging Agent.

Abstract

A novel organic/inorganic hybrid nanovesicle as an ultrasound imaging agent is synthesized via facile emulsion and silica deposition methods. This nanovesicle, hyaluronate (HA)-docetaxel (DTX)/perfluoro-n-pentane (PFP)@SNC, consists of an encapsulated liquid PFP core, loaded DTX, and an HA-decorated silica shell. The HA-DTX/PFP@SNC has a narrow size distribution of 274.5 ± 3.25 nm, a negative zeta potential of -11.6 ± 0.47 mV, and an entrapment efficiency of 86.70% ± 1.42%. HA-DTX/PFP@SNC possesses an ultrasound (US)-triggered drug release and a temperature-dependent size change behavior. Compared with DTX/PFP@soybean phosphatidylcholine (SPC), which has no silica shell, the HA-DTX/PFP@SNC is more stable under various conditions. The MTT assay indicates that the blank HA-PFP@SNC vehicle has no cytotoxicity to A549 cells. Furthermore, due to the HA-mediated tumor-targeting ability, the HA-DTX/PFP@SNC shows obvious cytotoxicity to A549 cells. In vitro and in vivo US imaging results indicate that HA-DTX/PFP@SNC has a stronger and more durable echo signal than DTX/PFP@SPC. Moreover, the in vivo echo signal of HA-DTX/PFP@SNC is stronger than that of DTX/PFP@SNC due to the HA-mediated tumor targeting. Therefore, this novel organic/inorganic hybrid vesicle is a US contrast agent candidate.