Design and Biodistribution of PEGylated Core-Shell X-ray Fluorescent Nanoparticle Contrast Agents

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Radiology

Background:

• Nanoparticle (NP) accumulation in organs like the liver and spleen hinders targeted delivery for bioimaging and therapeutics.
• Polyethylene glycol (PEG) surface functionalization is a strategy to reduce NP sequestration, but its in vivo stability and biodistribution impact require further investigation.
• X-ray fluorescence (XRF) imaging offers noninvasive, quantitative in vivo mapping of elemental biodistribution with high resolution and penetration.

Purpose of the Study:

• To investigate the role of chemisorbed versus physisorbed PEG on silica-coated molybdenum-based contrast agents in affecting their in vivo biodistribution.
• To quantitatively assess the impact of PEGylation strategies on nanoparticle uptake by organs using whole-body XRF imaging.
• To establish a foundation for developing strategies to mitigate undesired nanoparticle uptake.

Main Methods:

• Stepwise layering approach for synthesizing silica-coated molybdenum-based contrast agents.
• Whole-body XRF imaging for noninvasive, quantitative in vivo biodistribution analysis.
• Comparative studies using physisorbed PEG (1.5 kDa) and chemisorbed mPEG-Si (6-9 PEG units).
• Multiscale imaging with fluorophore-doped silica shells for microscopic validation.

Main Results:

• Physisorbed PEG did not significantly alter nanoparticle biodistribution.
• Chemisorbed PEG significantly reduced NP uptake in the liver.
• The spleen compensated for reduced liver sequestration, as validated microscopically.
• XRF imaging proved effective for rapid, quantitative in vivo pharmacokinetic assessment of functionalized contrast agents.

Conclusions:

• The method of PEG attachment (chemisorption vs. physisorption) critically influences nanoparticle biodistribution in vivo.
• Chemisorption of PEG offers a promising strategy to reduce liver sequestration of nanoparticles.
• XRF imaging is a valuable tool for evaluating nanoparticle surface modifications and guiding the development of targeted delivery systems.