Biodegradable Iron Oxide Clusters for MRI Contrast
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Solution Overview
Problem
Current methods for diagnosing microthrombi in ischemic stroke patients are inadequate due to the lack of reliable, non-invasive detection techniques, leading to incomplete microvascular reperfusion and significant human and economic costs, with existing molecular imaging tools facing challenges of toxicity and low contrast signals.
Innovation Solution
Development of biodegradable iron oxide particles with a hydrodynamic diameter between 200 nm and 2000 nm, coated with polycathecolamine or polyserotonine, which accumulate at microthrombi sites and provide enhanced contrast for MRI while being metabolized safely within the body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If one uses one-micrometer diameter iron particles for molecular imaging, then the contrast signal is strong enough for reliable detection, but the particles accumulate in tissue from the mononuclear phagocytic system and do not degrade, causing lysosomal dysfunction and tissue vacuolation (toxicity)
Solution Approach 1:
The patent divides the iron oxide into nanoparticles (10-150 nm) rather than using bulk one-micrometer particles. This segmentation maintains sufficient magnetic contrast while enabling safe metabolism through the mononuclear phagocytic system, resolving the contradiction between signal strength and toxicity.
Solution Approach 2:
The patent changes the size parameter of iron oxide particles from one micrometer to 10-150 nanometers. This parameter change allows the particles to be metabolized by the MPS while maintaining adequate contrast for molecular imaging, eliminating the toxicity issue of larger particles.
2Object-affected harmful factors
If one uses smaller diameter SPIO particles (10-150 nm) for biocompatibility and metabolisation, then the particles are safely degraded by the mononuclear phagocytic system, but the contrast is too low to provide a reliable signal in T2* weighted MRI
Solution Approach 1:
The patent merges multiple small SPIO nanoparticles (10-150 nm) into clusters of 10-100 nanoparticles aggregated together. This merging maintains the biocompatibility and metabolizable nature of small particles while accumulating sufficient magnetic contrast to produce reliable T2* weighted MRI signals.
Solution Approach 2:
The patent creates composite structures consisting of multiple iron oxide nanoparticles aggregated within a biodegradable polymer matrix. This composite approach combines the advantages of small particles (biocompatibility) with sufficient contrast signal, resolving the contradiction between safety and detectability.
3Measurement precision
If one uses a larger diameter for iron oxide particles to ensure reliable molecular imaging contrast, then the contrast signal is sufficient for T2* weighted MRI detection, but the particles are not properly metabolized and accumulate in tissue
Solution Approach 1:
The patent segments the iron oxide into multiple small nanoparticles (10-150 nm) rather than using a single large particle. This segmentation ensures proper metabolism by the mononuclear phagocytic system while the aggregated cluster provides sufficient contrast signal for reliable imaging.
Solution Approach 2:
The patent changes the size parameter to 10-150 nm for individual nanoparticles, which are metabolizable, while using aggregates of 10-100 particles to achieve sufficient contrast. This parameter optimization resolves the contradiction between imaging reliability and biodegradability.
4Measurement precision
If one uses one-micrometer diameter iron particles for imaging, then the contrast signal is strong, but the particles cause liver dysfunction due to accumulation in the mononuclear phagocytic system
Solution Approach 1:
The patent segments iron oxide into small nanoparticles (10-150 nm) that can be properly metabolized by the mononuclear phagocytic system, preventing accumulation in the liver and associated dysfunction, while maintaining adequate imaging contrast through aggregation.
Solution Approach 2:
The patent changes the particle size parameter from one micrometer to 10-150 nanometers, enabling safe metabolism and preventing liver accumulation, while using aggregated clusters to maintain sufficient contrast signal for imaging.
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 particles effectively target and visualize microthrombi, enabling improved diagnosis and monitoring of thrombolysis therapy, reducing the risk of adverse effects and improving patient outcomes.
Implementation Method 1
The MPIO accumulate at the area of the targeted disease epitope expression and reveal the pathology in T2* weighted MRI thanks to their superparamagnetic properties
Implementation Method 2
The clusters provide similar contrast to that of the MPIO and rapidly disassemble into isolated SPIO particles once they reach the acidic lysosomal compartment of the MPS cells, thus enabling their digestion
Data Source
AI summary
The present invention relates to novel biocompatible imaging particles comprising superparamagnetic iron oxide (SPIO) assembled into submicromiter-sized clusters within a biodegradable polycathecolamine or polyserotonine matrix, their synthesis and use in imaging techniques. These particles overcome the issues of toxicity and unreliable signal of the molecules from the prior art by providing similar contrast to that of the microparticles of iron oxide and rapidly disassemble into isolated SPIO particles once they reach the acidic lysosomal compartment of the MPS cells, thus enabling their digestion. The present invention is thus directed to a particle having a hydrodynamic diameter comprised between 100 nm and 2000 nm, said particle comprising nanoparticles of iron oxide embedded within a matrix of polycathecolamine or polyserotonine, each of said nanoparticles of iron oxide being coated by a polymer which is different from polycathecolamine or polyserotonine