Ultrafine Gadolinium POS Nanoparticles for High-Relaxivity MRI
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing nanoparticles used for medical imaging and therapy face challenges such as low contrast, non-specificity, rapid renal excretion, field-dependent properties, and limited accessibility, especially for tumors, due to their size and composition, which affects their efficacy and safety.
Innovation Solution
Development of ultrafine nanoparticles with a polyorganosiloxane matrix and metal complexes, specifically rare earth cations, chelating agents, and functionalizing grafts, allowing for sizes under 20 nm, high loading, and enhanced biocompatibility, stability, and accessibility, enabling multimodal imaging and therapeutic functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If molecular contrast agents are used, then renal elimination is good, but local concentration of contrast agent is low and contrast is insufficient
Solution Approach 1:
The patent combines multiple gadolinium complexes within a single nanoparticle structure, merging the functions of multiple contrast agents into one entity. This allows high local concentration of gadolinium (improving contrast) while maintaining a size suitable for renal elimination.
Solution Approach 2:
The patent employs a nested structure where gadolinium complexes are embedded within a polyorganosiloxane matrix. The metal complexes are positioned inside the matrix structure, creating a hierarchical organization that concentrates contrast agents while controlling overall particle size.
2Length of moving object
If nanoparticle size is reduced to improve accessibility and renal elimination, then biodistribution improves, but manufacturing precision and stability become more difficult to control
Solution Approach 1:
The patent systematically varies parameters such as the degree of crosslinking, metal complex concentration, and polyorganosiloxane composition to optimize nanoparticle size. By controlling these parameters, the patent achieves consistent sizes in the 1-20 nm range while maintaining stability and manufacturability.
Solution Approach 2:
The patent creates composite nanoparticles combining polyorganosiloxane matrix with metal complexes. This composite structure provides both the small size needed for renal elimination and the stability required for manufacturing control, as the matrix protects the metal complexes while maintaining a defined particle architecture.
3Quantity of substance
If high concentration of metal complexes is loaded into nanoparticles, then contrast and therapeutic effect improve, but toxicity may increase
Solution Approach 1:
The polyorganosiloxane matrix acts as an intermediary between the metal complexes and the biological environment. It allows high loading of metal complexes for improved contrast and therapy while protecting against toxicity by controlling the release and interaction of metal ions with biological systems.
Solution Approach 2:
The patent creates local concentration of metal complexes within the nanoparticle matrix, providing high contrast and therapeutic effect at the target site while maintaining low overall concentration in the body. The metal complexes are localized within the matrix structure, providing high local quality where needed while minimizing systemic toxicity.
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 nanoparticles provide improved contrast, accessibility, and safety by ensuring high relaxivity, favorable biodistribution, and reduced toxicity, facilitating targeted therapy and imaging, particularly in MRI, while maintaining stability and compatibility in biological media.
Implementation Method 1
a chelating functionalizing graft C1 which is: derived from a chelating agent C1, bound to the POS matrix by an —Si—C— covalent bond, and in sufficient quantity to be able to complex all the cations Mn+
Implementation Method 2
positive T1 and negative T2 contrast agents... which permit lightening of the image as contact of water with the contrast agent makes it possible to reduce the longitudinal relaxation time: T1
Implementation Method 3
Dissolution of the cores by means of a pH modifier and/or of a chelating agent C2, identical to or different from C1, that is able to complex some or all of the cations Mn+
Implementation Method 4
Dissolution of the cores by means of a pH modifier and/or of a chelating agent C2, identical to or different from C1, that is able to complex some or all of the cations Mn+
Data Source
AI summary
The invention relates to novel biocompatible hybrid nanoparticles of very small size, useful in particular for diagnostics and/or therapy.The purpose of the invention is to offer novel nanoparticles which are useful in particular as contrast agents in imaging (e.g. MRD and/or in other diagnostic techniques and/or as therapeutic agents, which give better performance than the known nanoparticles of the same type and which combine both a small size (for example less than 20 nm) and a high loading with metals (e.g. rare earths), in particular so as to have, in imaging (e.g. MRI), strong intensification and a correct response (increased relaxivity) at high frequencies.Thus, the nanoparticles according to the invention, with diameter d1 between 1 and 20 nm, each comprise a polyorganosiloxane (POS) matrix including gadolinium cations optionally associated with doping cations; a chelating graft C1 DTPABA (diethylenetriaminepentaacetic acid bisanhydride) bound to the POS matrix by an —Si—C— covalent bond, and present in sufficient quantity to be able to complex all the gadolinium cations; and optionally another functionalizing graft Gf* bound to the POS matrix by an —Si—C— covalent bond (where Gf* can be derived from a hydrophilic compound (PEG); from a compound having an active ingredient PA1; from a targeting compound; from a luminescent compound (fluorescein).The method for the production of these nanoparticles and the applications thereof in imaging and in therapy also form part of the invention.