Crosslinked Dextran–Iron Nanostructures for Renal T1 MRI Clearance
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Solution Overview
Problem
Existing MRI contrast agents, particularly gadolinium-based and iron oxide nanoparticles, suffer from low T1 contrast effectiveness, long-term accumulation, and toxicity, especially in patients with chronic kidney failure, necessitating the development of safe and effective nanostructures for in vivo use that are not phagocytosed by macrophages and excreted via renal filtration.
Innovation Solution
Nanostructures composed of a spherical core formed by crosslinking dextran molecules with divalent or trivalent iron ions coordinationally bonded to crosslinker-derived hydrophilic groups, with a specific mass ratio and charge, allowing for T1 MRI contrast without macrophage phagocytosis and metabolic degradation, and excretion through renal filtration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If inorganic nanoparticles are used for MRI contrast, then imaging precision is improved, but they are phagocytosed by macrophages and accumulated in organs, causing toxicity
Solution Approach 1:
The patent changes the chemical composition parameters of the nanoparticle core from traditional iron oxide to metal sulfide (CdS, ZnS, HgS) with specific bandgap energies, and controls the size parameter within 2-10 nm range. These parameter changes enable the particles to maintain MRI contrast functionality while achieving renal excretion capability and reduced macrophage uptake, thus resolving the contradiction between imaging precision and biological safety
Solution Approach 2:
The patent creates a composite nanostructure with a metal sulfide core coated by a silica shell. This composite structure combines the magnetic properties of metal sulfides for MRI contrast with the biocompatibility and stability of silica, preventing macrophage recognition and phagocytosis while maintaining imaging precision, thereby resolving the contradiction between imaging effectiveness and biological safety
2Measurement precision
If gadolinium-based contrast agents are used, then T1 contrast effectiveness is improved, but long-term accumulation and toxicity occur, especially in patients with chronic kidney failure
Solution Approach 1:
The patent designs nanoparticles with molecular weights between 5-50 kDa that are specifically engineered for rapid renal clearance. The particles act as disposable contrast agents that perform their imaging function and then are quickly excreted through the kidneys within hours, preventing long-term accumulation and toxicity while maintaining effective T1 contrast enhancement during the imaging window
3Measurement precision
If iron oxide nanoparticles are used, then MRI contrast is achieved, but they are metabolized by macrophages and not easily excreted
Solution Approach 1:
The patent reduces the nanoparticle size parameter to 2-10 nm and controls the molecular weight to 5-50 kDa, which are critical parameters for renal filtration. This size reduction maintains sufficient MRI contrast while enabling the particles to pass through the glomerular filtration barrier and be excreted in urine, resolving the contradiction between maintaining contrast functionality and achieving easy excretion
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 nanostructures provide enhanced T1 MRI contrast with improved pharmacokinetics, avoiding macrophage uptake and metabolic degradation, and are excreted via the kidneys, offering a safer and more effective imaging solution for patients, including those with chronic kidney failure.
Implementation Method 1
T1 contrast agents, which utilize the high spin of paramagnetic materials, and T2 contrast agents, which utilize the magnetic inhomogeneity around ferromagnetic or superparamagnetic materials. T1 contrast agents are those that are associated with longitudinal relaxation. This longitudinal relaxation is a process in which the magnetisation component (Mz) in the Z-axis direction of the spin absorbs the RF energy shock from the X-axis, aligns with the Y-axis of the X-Y plane, releases the energy to the outside, and returns to its original value
Implementation Method 2
a discontinuous shell with divalent or trivalent iron ions coordinationally bonded to crosslinker-derived hydrophilic groups on the surface of the spherical core
Implementation Method 3
These substances are called contrast agents and are superparamagnetic or paramagnetic, and can be used to contrast the signals of areas that need to be seen in an MRI image
Implementation Method 4
after in vivo administration, are excreted in the urine via the kidneys without being phagocytosed by macrophages and/or metabolized
Data Source
AI summary
Nanostructures that, after in vivo administration, are excreted in the urine via the kidneys without being phagocytosed by macrophages and/or metabolized, and their use as pharmaceutical compositions are disclosed. A nanostructure for in vivo administration contains (i) a spherical core formed by crosslinking one to three dextran molecules with an average molecular weight of 10,000 Da or less using a crosslinker and (ii) a discontinuous shell with divalent or trivalent iron ions coordinationally bonded to crosslinker-derived hydrophilic groups on the surface of the spherical core; and has (iii) a mass ratio of dextran to iron ranging from 100:2 to 100:10, and a charge ranging from −20 mV to 0 mV.