Cross-Modal Imaging Reveals Nanoparticle Uptake Dynamics in Hematopoietic Bone Marrow during Inflammation

Area of Science:

• Immunology
• Biomedical Imaging
• Nanotechnology

Background:

• Innate immune cells respond rapidly to inflammation, with bone marrow supporting their turnover.
• The impact of inflammation on nanoparticle uptake by innate immune cell progenitors in bone marrow is not well understood.
• Developing imaging tools is crucial to investigate nanoparticle dynamics in inflamed bone marrow.

Purpose of the Study:

• To develop imaging tools for exploring nanoparticle uptake in the bone marrow niche during inflammation.
• To investigate the dynamics of fluorescently labeled cross-linked iron oxide nanoparticles in inflamed bone marrow.

Main Methods:

• Induction of moderate and intense inflammation models in mice using lipopolysaccharide and streptozotocin.
• In vivo magnetic resonance imaging (MRI) and fluorescence imaging to assess nanoparticle distribution.
• Intravital microscopy to observe nanoparticle colocalization with monocytes in the bone marrow.

Main Results:

• Increased nanoparticle uptake in the bone marrow correlated with elevated inflammation levels.
• Enhanced permeability and retention in the inflamed marrow led to increased nanoparticle intake by hematopoietic progenitor cells.
• Greater colocalization of nanoparticles with monocytes was observed in inflamed marrow niches.

Conclusions:

• Inflamed hematopoietic bone marrow enhances nanoparticle storage and deployment, targeting innate immune cells at their origin.
• The hematopoietic bone marrow plays a critical role in distributing iron nanoparticles to innate immune cells during inflammation.
• The hematopoietic bone marrow serves as a potential imaging biomarker for early inflammation detection.