Core/Shell Nanoparticles for X-ray CT Imaging Agents
Find Innovative SolutionsGenerate Solutions
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 systems suffer from synthesis issues and cost inefficiencies.
Innovation Solution
Development of core/shell nanoparticles with an active heavy metal core and a passive nanoshell, designed to enhance CT contrast and targeting capabilities, with a mean diameter optimized for kidney clearance, using materials like tantalum oxide and polymeric shells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If standard CT imaging agents (iodinated benzoic acid derivatives) are used, then imaging function is provided, but they clear from the body very rapidly making it difficult to target disease sites
Solution Approach 1:
The patent employs composite nanoparticle structures combining heavy metal cores (providing X-ray attenuation) with polymer shells (providing circulation stability and targeting functionality). This composite approach enables both prolonged blood half-life and enhanced targeting capability that neither component could achieve alone.
Solution Approach 2:
The patent modifies the physical and chemical parameters of imaging agents by transitioning from small molecular weight iodinated compounds to nanoparticle formulations with controlled size distribution (mean diameter 5-50 nm). This parameter change extends blood circulation time while enabling disease site accumulation through enhanced permeability and retention effects.
2Quantity of substance
If nanoparticles of elemental (zerovalent) metal species are used, then highest density (number of heavy metal atoms/volume) is achieved, but they suffer from robust synthesis issues and instability due to oxidation
Solution Approach 1:
The patent introduces polymer shells as intermediary protective layers surrounding heavy metal cores. These shells act as barriers preventing oxidation of the metal atoms while maintaining high heavy metal atom density. The shell also provides a stable interface for synthesis and functionalization.
Solution Approach 2:
By combining heavy metal atoms (for high density and X-ray attenuation) with stable polymer materials (for oxidation resistance and synthesis robustness), the patent creates composite nanoparticles that overcome the limitations of elemental metal nanoparticles while preserving their high density advantage.
3Reliability
If nanoparticles of inert metals such as gold are used, then synthesis and stability issues are overcome, but they are not very cost effective
Solution Approach 1:
The patent changes the material composition parameter by replacing expensive inert metals like gold with more cost-effective heavy metals (e.g., barium, lanthanum, gadolinium) that provide equivalent or superior X-ray attenuation. This substitution maintains synthesis robustness and stability while significantly reducing material costs.
Solution Approach 2:
The patent adopts cheaper heavy metal alternatives that, while potentially less inert than gold, provide sufficient stability when encapsulated in polymer shells. This approach reduces manufacturing cost while maintaining adequate reliability for diagnostic imaging applications.
4Quantity of substance
If a greater number of heavy metal atoms are delivered to target tissues, then image contrast enhancement is improved, but synthesis robustness and cost effectiveness deteriorate
Solution Approach 1:
The patent segments the imaging agent into discrete nanoparticle units, each containing a high concentration of heavy metal atoms in the core. This segmentation allows delivery of large numbers of heavy metal atoms to target tissues while maintaining controlled synthesis through standardized nanoparticle production methods and reducing per-dose cost through efficient packaging of multiple atoms per particle.
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 high-density atoms for improved CT contrast, increased blood half-life, and targeted disease site delivery, while being cost-effective and reducing toxicity.
Implementation Method 1
The nanoparticle core comprises at least one heavy metal element in a non-zero valent state... operable for use as an imaging agent in X-ray/computed tomography
Implementation Method 2
operable for use as an imaging agent in X-ray/computed tomography
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. Included herein are methods for forming such agents, comprising forming an ensemble of core/shell nanoparticles, wherein the mean diameter of the ensemble of core/shell nanoparticles is selected so as to render the nanoparticles in the ensemble substantially clearable by a mammalian kidney.