Tantalum Oxide Core/Shell Nanoparticles for CT Imaging
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Solution Overview
Problem
Current X-ray/computed tomography (CT) imaging agents, such as iodinated benzoic acid derivatives, face challenges including rapid clearance from the body, limited targeting capability, and toxicity, while nanoparticle-based systems struggle with robust synthesis, instability, and high costs, limiting their effectiveness in delivering high-density contrast agents to disease sites.
Innovation Solution
Development of core/shell nanoparticles with a tantalum oxide core in a non-zero valent state and a passive polymeric or ligand-based shell, designed to enhance CT contrast and targeting capabilities, with a focus on improved synthesis robustness and cost-effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If standard CT imaging agents (iodinated benzoic acid derivatives) are used, then imaging function is provided, but rapid clearance from body and limited targeting capability occur
Solution Approach 1:
The patent changes the physical state and molecular weight parameters by transitioning from low molecular weight iodinated compounds to high molecular weight nanoparticle systems. This parameter change extends blood half-life while the nanoparticle surface can be functionalized with targeting moieties to provide targeting capability simultaneously
Solution Approach 2:
The patent employs composite nanoparticle structures combining heavy metal atoms (for contrast enhancement) with polymeric or ligand-based shells (for stability and targeting). This composite approach allows simultaneous achievement of extended circulation time and targeting functionality through the shell components
2Quantity of substance
If nanoparticles of elemental metal species are used, then highest density (number of heavy metal atoms/volume) is achieved, but robust synthesis and instability due to oxidation occur
Solution Approach 1:
The patent creates a chemically inert environment by coating reactive metal atoms with oxide shells or stabilizing ligands. This protective shell prevents oxidation and instability while maintaining the high density of heavy metal atoms in the core, resolving the contradiction between quantity and reliability
Solution Approach 2:
The patent uses composite structures where a core of metal atoms provides high density, while an outer shell of oxide or stabilizing ligands provides chemical stability and prevents oxidation. This composite material approach simultaneously achieves both high heavy metal atom quantity and reliability
3Reliability
If nanoparticles of inert metals such as gold are used, then stability issues are overcome, but cost effectiveness deteriorates
Solution Approach 1:
The patent changes the material composition parameter by using less expensive metals (such as iron, manganese, or other transition metals) instead of expensive inert metals like gold. Combined with oxide shell formation or ligand stabilization, this parameter change maintains stability while improving cost effectiveness
4Quantity of substance
If larger number of heavy metal atoms are delivered to target tissues, then image contrast enhancement is improved, but toxicity and radiation dose concerns increase
Solution Approach 1:
The patent applies local quality by concentrating heavy metal atoms within nanoparticle cores for maximum contrast enhancement at the target site, while the surface of the nanoparticle is covered with biocompatible materials that reduce toxicity. This spatial differentiation allows high contrast without proportional increase in systemic toxicity
Solution Approach 2:
The patent uses biocompatible shell coatings (polymeric or ligand-based) that form protective films around the heavy metal core. These shells reduce toxicity and control radiation dose distribution while allowing the high density core to provide superior image contrast enhancement
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The core/shell nanoparticles effectively deliver a large number of high-density tantalum atoms, enhancing CT contrast and allowing for targeted imaging and increased blood half-life, while maintaining biocompatibility and reducing toxicity.
Implementation Method 1
The present invention is directed to core/shell nanoparticles... operable for use as an imaging agent in X-ray imaging, particularly computed tomography (CT) imaging
Data Source
AI summary
The present invention is generally directed to core/shell nanoparticles, wherein such core/shell nanoparticles comprise a nanoparticle core and a nanoshell disposed about the nanoparticle core such that, in the aggregate, they form a core/shell nanoparticle that is operable for use as an imaging agent in X-ray/computed tomography (CT). Typically, such core/shell nanoparticle-based X-ray CT imaging agents further comprise a targeting species for targeting the imaging agent to diseased sites.