Gold/silica nanoparticles with a near-infrared fluorescent and PEGylated paramagnetic lipid coating

The gold/silica nanoparticle with a near-infrared (NIR) fluorescent and PEGylated paramagnetic lipid coating, abbreviated as Au-SiFluPaLCs, is a trimodal imaging agent that has been developed by van Schooneveld et al. for combined magnetic resonance imaging (MRI), computed tomography (CT), and optical imaging (1). The idea of using multiple modalities in a single imaging session comes from the fact that imaging modalities with high sensitivity have relatively poor resolution, while those with high resolution have relatively poor sensitivity (2, 3). Integration of multiple modalities in imaging would combine the advantages of each modality and allow better characterization of diseases and disease processes (4). Development of hybrid imaging technology has also triggered great effort in the development of multimodal imaging agents to boost the benefits of hybrid instrument technology (5, 6). In principle, the synthesis of multimodal agents is similar to that of single-mode agents (6). A large molecule is usually necessary for efficient labeling and delivery of multiple reporters. Intensively investigated large molecules include liposomes, dendrimers, polymers, and endogenous nanoparticles (6, 7). In the case of liposomes, reporters are either encapsulated in the aqueous interior space or incorporated into the lipid bilayer (1, 8). The latter approach usually results in an improved ionic relaxivity of the MRI metals. In the development of multimodal agents, questions arise from the multistep conjugations that often lead to a low chemical yield. The presence of different molecules on the same nanoparticle surface may interfere with the targeting capabilities and the subsequent intracellular uptake of the agents. The optimization of multimodal imaging agents is more challenging in terms of immunogenicity, toxicity, specificity, interference with biological processes, and accumulation in target organs (5, 6). van Schooneveld et al. and Koole et al. synthesized a series of multimodal imaging agents by coating silica particles with a dense monolayer of PEGylated paramagnetic lipids without the use of coupling agents (1, 8, 9). The presence of a dense lipid layer around the inorganic core renders these particles stable in aqueous dispersion and bioapplicable. The lipid coating also allows for conjugation of target-specific molecules at the surface of nanoparticles. These agents include Q-SiPaLCs, RGD-conjugated Q-SiPaLCs, and Au-SiFluPaLCs. Of these agents, Au-SiFluPaLCs was synthesized as a trimodal contrast agent for combined MRI, CT, and optical imaging (1). This trimodal agent is composed of a gold/silica particle core with a NIR fluorescent and PEGylated paramagnetic lipid coating. The electron-dense gold core enables its detection with CT, while the paramagnetic lipids generate the MRI signal and the NIR dye Cy5.5 allows for optical imaging. The results obtained with Au-SiFluPaLCs have shown that the trimodal agent effectively labels phagocytotic cells and mouse liver cells . This agent can be a useful tool in a multitude of applications, including cell tracking and targeted molecular imaging (1). This chapter summarizes the data obtained with Au-SiFluPaLCs. Another chapter in MICAD summarizes the data obtained with Q-SiPaLCs.