Radiopaque Iodosilane-Coated Lipid Hybrid Nanoparticle Contrast Agent for Dual-Modality Ultrasound and X-ray Bioimaging

Abstract

Here, we report the synthesis of robust hybrid iodinated silica–lipid nanoemulsions (HSLNEs) for use as a contrast agent for ultrasound and X-ray applications. We engineered iodinated silica nanoparticles (SNPs), lipid nanoemulsions, and a series of HSLNEs by a low-energy spontaneous nanoemulsification process. The formation of a silica shell requires sonication to hydrolyze and polymerize/condensate the iodomethyltrimethoxysilane at the oil/water interface of the nanoemulsion droplets. The resulting nanoemulsions (NEs) exhibited a homogeneous spherical morphology under transmission electron microscopy. The particles had diameters ranging from 20 to 120 nm with both negative and positive surface charges in the absence and presence of cetyltrimethylammonium bromide (CTAB), respectively. Unlike CTAB-coated nanoformulations, the CTAB-free NEs showed excellent biocompatibility in murine RAW macrophages and human U87-MG cell lines in vitro. The maximum tolerated dose assessment was evaluated to verify their safety profiles in vivo. In vitro X-ray and ultrasound imaging and in vivo computed tomography were used to monitor both iodinated SNPs and HSLNEs, validating their significant contrast-enhancing properties and suggesting their potential as dual-modality clinical agents in the future.

Recent Advancements in Ultrasound Contrast Agents Based on Nanomaterials for Imaging

“…This improves the robustness and homogeneity of the resulting particles with high quantities of iodine affording efficient bimodal X-ray and USI agents (Figure 7B). 156 All of these parameters of the designed NEs render them appealing candidates for clinical biomedical imaging, such as avoiding rapid renal elimination that might cause kidney failure, improving the contrast efficiency, and reducing toxicity.…”

Radiopaque, Self-Immolative Poly(benzyl ether) as a Functional X-ray Contrast Agent: Synthesis, Prolonged Visibility, and Controlled Degradation

“…In the chemical design of imaging agents, organic materials provide greater biocompatibility and synthetic versatility in comparison to inorganic materials. Also, to overcome the low electron density of these materials, a variety of iodinated small-molecule agents have been explored because the innermost electron of iodine strongly absorbs diagnostic X-rays. , As a result, most of the iodinated agents include ionic (e.g., Diatrizoate and Ioxaglate) or nonionic (e.g., Iohexol and Iodixanol) aromatic small-molecule forms and can be injected through intravenous routes or loaded into carriers, such as emulsions, liposomes, hydrogels, or particles. − Although these agents have achieved the desired properties under physiological conditions and have been commercialized, they still suffer from a rapid excretion rate and nonspecificity, limiting their potential in other biorelated fields. − As an alternative, polymeric materials have been investigated by taking advantage of their structural diversification, tunable functionality, and intrinsically high molecular weight. In general, iodinated motifs are conjugated on predesigned backbones or directly polymerized, which provides a platform for the development of multifunctional nanoparticles and implantable devices that require X-ray visibility for in situ monitoring. − However, the stable covalent backbone generally reduces the biodegradability of polymeric materials when they reach the end of their usefulness.…”