Paramagnetic lipid-coated silica nanoparticles with a fluorescent quantum dot core: a new contrast agent platform for multimodality imaging.

Silica particles as a nanoparticulate carrier material for contrast agents have received considerable attention the past few years, since the material holds great promise for biomedical applications. A key feature for successful application of this material in vivo is biocompatibility, which may be significantly improved by appropriate surface modification. In this study, we report a novel strategy to coat silica particles with a dense monolayer of paramagnetic and PEGylated lipids. The silica nanoparticles carry a quantum dot in their center and are made target-specific by the conjugation of multiple alphavbeta3-integrin-specific RGD-peptides. We demonstrate their specific uptake by endothelial cells in vitro using fluorescence microscopy, quantitative fluorescence imaging, and magnetic resonance imaging. The lipid-coated silica particles introduced here represent a new platform for nanoparticulate multimodality contrast agents.

Imaging and quantifying the morphology of an organic-inorganic nanoparticle at the sub-nanometre level.

The development of hybrid organic-inorganic nanoparticles is of interest for applications such as drug delivery, DNA and protein recognition, and medical diagnostics. However, the characterization of such nanoparticles remains a significant challenge due to the heterogeneous nature of these particles. Here, we report the direct visualization and quantification of the organic and inorganic components of a lipid-coated silica particle that contains a smaller semiconductor quantum dot. High-angle annular dark-field scanning transmission electron microscopy combined with electron energy loss spectroscopy was used to determine the thickness and chemical signature of molecular coating layers, the element atomic ratios, and the exact positions of different elements in single nanoparticles. Moreover, the lipid ratio and lipid phase segregation were also quantified.

A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT and fluorescence imaging.

An important challenge in medical diagnostics is to design all-in-one contrast agents that can be detected with multiple techniques such as magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET), single photon emission tomography (SPECT) or fluorescence imaging (FI). Although many dual labeled agents have been proposed, mainly for combined MRI/FI, constructs for three imaging modalities are scarce. Here gold/silica nanoparticles with a poly(ethylene glycol), paramagnetic and fluorescent lipid coating were synthesized, characterized and applied as trimodal contrast agents to allow for nanoparticle-enhanced imaging of macrophage cells in vitro via MRI, CT and FI, and mice livers in vivo via MRI and CT. This agent can be a useful tool in a multitude of applications, including cell tracking and target-specific molecular imaging, and is a step in the direction of truly multi-modal imaging.

Improved biocompatibility and pharmacokinetics of silica nanoparticles by means of a lipid coating: a multimodality investigation.

Silica is a promising carrier material for nanoparticle-facilitated drug delivery, gene therapy, and molecular imaging. Understanding of their pharmacokinetics is important to resolve bioapplicability issues. Here we report an extensive study on bare and lipid-coated silica nanoparticles in mice. Results obtained by use of a wide variety of techniques (fluorescence imaging, inductively coupled plasma mass spectrometry, magnetic resonance imaging, confocal laser scanning microscopy, and transmission electron microscopy) showed that the lipid coating, which enables straightforward functionalization and introduction of multiple properties, increases bioapplicability and improves pharmacokinetics.

Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe.

MRI detectable and targeted quantum dots were developed. To that aim, quantum dots were coated with paramagnetic and pegylated lipids, which resulted in a relaxivity, r(1), of nearly 2000 mM(-1)s(-1) per quantum dot. The quantum dots were functionalized by covalently linking alphavbeta3-specific RGD peptides, and the specificity was assessed and confirmed on cultured endothelial cells. The bimodal character, the high relaxivity, and the specificity of this nanoparticulate probe make it an excellent contrast agent for molecular imaging purposes.