Ultrasmall Surface-Charge-Modified Tantalum Oxide Nanoparticles for the Assessment of Articular Cartilage Using Contrast-Enhanced Computed Tomography

TL;DR

Researchers developed tiny tantalum oxide nanoparticles that can detect cartilage damage and assess joint health using CT scans.

Contribution

Ultrasmall tantalum oxide nanoparticles with tunable surface charge enable contrast-enhanced CT imaging of cartilage structure and lesions.

Findings

Positively charged Ta2O5-cNPs diffuse into cartilage and correlate with early osteoarthritis indicators.

Neutral Ta2O5-nNPs remain on cartilage surfaces, enhancing lesion detection and boundary contrast.

Both nanoparticle types successfully imaged cartilage in human and animal models.

Abstract

The size and surface
properties of nanoparticles (NPs)
define their
interactions with biological tissues and impact their effectiveness
for targeted imaging and therapeutic applications. Here, we investigate
ultrasmall tantalum oxide nanoparticles (Ta2O5-NPs) as computed tomography (CT) contrast agents and the effects
of NP surface charge on diffusion in ex vivo human
cartilage samples, as well as after intra-articular administration
in intact rabbit and equine joints. Controlled hydrolysis of tantalum­(V)
ethoxide, followed by coating with positively charged trimethylammonium
and nonionic poly­(ethylene glycol) (PEG) ligands at different ratios,
affords the approximately 3 nm positively charged (Ta2O5-cNPs) and neutral (Ta2O5-nNPs) tantalum
oxide nanoparticles. Ta2O5-cNPs readily diffuse
into human cartilage as measured by microcomputed tomography, and
the Ta2O5-cNPs partition positively correlates
with key indicators of early-stage osteoarthritis to include the proteoglycan
content, equilibrium Young’s modulus, and porosity (stress-relaxation
time constant) while inversely with viscosity (phase shift). In contrast,
the neutral Ta2O5-nNPs reside at the cartilage
surface, triple the attenuation difference at the cartilage–fluid
boundary, accumulate within microscopic surface injuries, and enable
clear detection of surface injuries and lesions. When extended to
intact ex vivo animal models, Ta2O5-cNPs diffuse into rabbit knee cartilage over 24 h, while
Ta2O5-nNPs delineate fissures and partial erosions
in equine carpal cartilage. In conclusion, customizing the Ta2O5-NPs surface charge allows, or prevents, their
diffusion into cartilage, enabling distinct CT imaging applications:
diffusible Ta2O5-cNPs assess the cartilage structure
and function, while nondiffusible Ta2O5-nNPs
enhance cartilage segmentation and detect lesions in both human in vitro and animal ex vivo models.

Figures