Alpha-Hydroxyphosphonic Acid Conjugates for Nanoparticle Surface Modification
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Solution Overview
Problem
Transition metal oxide nanoparticles lack hydrophilicity, leading to instability in aqueous suspensions, particularly in applications like MRI and X-ray imaging, where monodisperse and stable particle size distribution is crucial, and existing surface treatments like silane can cause self-condensation and undesirable interactions with biological tissues.
Innovation Solution
Conjugating α-hydroxyphosphonic acid with a hydrophilic moiety, such as ethylene oxide units, to create nanoparticles that are hydrophilic and stable, maintaining all three hydroxyl groups for superior adhesion and neutral zeta potential, preventing interactions with human tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If transition metal oxide nanoparticles are used for imaging applications, then they provide appropriate imaging properties for MRI and X-ray, but they lack hydrophilicity and cannot form stable aqueous suspensions
Solution Approach 1:
The patent applies composite materials by combining transition metal oxide nanoparticles with alpha-hydroxyphosphonic acid conjugates featuring ethylene oxide units. This creates a hybrid structure where the inorganic nanoparticle core provides imaging properties while the organic phosphonic acid conjugate layer provides hydrophilicity and colloidal stability in aqueous media.
Solution Approach 2:
The patent changes the surface chemical parameters of the nanoparticles by introducing alpha-hydroxyphosphonic acid conjugates with specific structural parameters (ethylene oxide units with m and p values of 1-5, n and o values of 0-5). This modifies the surface properties to achieve both hydrophilicity and stability in physiological conditions.
2Stability of the object's composition
If silane based surface treatments are applied to improve hydrophilicity, then the nanoparticles become more compatible with aqueous media, but they undergo self condensation that causes nonuniform aggregation and polydisperse particle size distribution
Solution Approach 1:
The patent extracts the problematic self-condensation property from silane-based treatments and replaces it with alpha-hydroxyphosphonic acid conjugates that do not undergo self-condensation. The phosphonic acid groups bind to the nanoparticle surface without cross-linking, maintaining monodisperse particle size distribution while providing the needed hydrophilicity.
3Stability of the object's composition
If phosphate based materials are used to impart hydrophilicity, then the nanoparticles show improved hydrophilic properties, but they do not display sufficient stability as colloidal suspension in 150 mM NaCl aqueous medium after filtration
Solution Approach 1:
The patent modifies the phosphate-based approach by introducing alpha-hydroxyphosphonic acid conjugates with specific structural parameters including ethylene oxide units and controlled chain lengths (m, p, n, o values). This parameter optimization provides both hydrophilicity and sufficient colloidal stability in physiological saline conditions after filtration.
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 hydrophilically modified nanoparticles form stable colloidal suspensions in aqueous media, maintaining particle size stability and avoiding tissue interactions, suitable for long-term use as contrast agents in diagnostic imaging.
Implementation Method 1
α-hydroxyphosphonic acid conjugates...linked via the carbon atom carrying the α-hydroxy group...give the conjugate superior adhesion to nanoparticles
Data Source
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Figure 6A~6F
AI summary
The present application discloses treating water insoluble nanoparticles, particularly nanoparticles of metals and metal compounds which find utility in diagnostic imaging such as MR and X-ray imaging, with an alpha- hydroxyphosphonic acid conjugate with a hydrophilic moiety to render the nanoparticles sufficiently hydrophilic to find utility in diagnostic imaging. Among the modified hydrophilic nanoparticles disclosed are those in which the hydrophilic moieties of the modifying conjugate are ethylene oxide based polymers and copolymers and zwitterions and the nanoparticles are composed of transition metal oxides such as superparamagnetic iron oxide and tantalum oxide. Disclosed are nanoparticles which are sufficiently hydrophilic to form stable aqueous colloidal suspensions. Also disclosed is diagnostic imaging such as MR and X-ray using the modified hydrophilic nanoparticles as contrast agents.