A tissue chamber chip for assessing nanoparticle mobility in the extravascular space

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Systemic injection of nanomedicines faces challenges in achieving uniform and deep penetration into diseased tissues.
• Understanding extravascular transport is crucial for developing effective nanomedicines.
• Current methods for studying nanoparticle transport are limited.

Purpose of the Study:

• To design and fabricate a 'Tissue Chamber' chip for studying extravascular transport of molecules and nanoparticles.
• To evaluate the influence of nanoparticle surface chemistry on diffusion within a collagen matrix.
• To validate the chip's utility by comparing in vitro results with ex vivo brain tissue experiments.

Main Methods:

• Fabrication of a 'Tissue Chamber' chip with a collagen slab and a microchannel.
• Fluorescent microscopy to track the dynamics of fluorescently labeled molecules and nanoparticles.
• Analysis of mean square displacements (MSD) to calculate diffusion coefficients.
• Validation using FITC-Dextran molecules of varying molecular weights and fluorescence recovery after photobleaching (FRAP).
• Testing of six nanoparticles (~200 nm hydrodynamic diameter) with different surface chemistries (PEGylation, hyaluronic acid).
• Ex vivo experiments using freshly excised brain tissue slices.

Main Results:

• Diffusion coefficients decreased with increasing molecular weight of FITC-Dextran.
• MSD-derived diffusion coefficients correlated well with FRAP measurements for small molecules.
• PEGylation of nanoparticles enhanced their diffusion in the collagen slab.
• Hyaluronic acid coating reduced nanoparticle mobility, proportional to the molecular weight of HA.
• Ex vivo experiments showed significantly lower diffusion coefficients but confirmed the trends observed in vitro.
• The 'Tissue Chamber' chip demonstrated effective and efficient testing of nanomedicine transport.

Conclusions:

• The 'Tissue Chamber' chip is a valuable tool for studying extravascular transport of nanomedicines.
• Nanoparticle surface chemistry significantly impacts diffusion in biological matrices.
• This model offers an efficient, animal-minimizing approach for nanomedicine evaluation.