Carboxylated Mannan Coating for MRI Contrast Agent Stability

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Solution Overview

Problem

Existing MRI contrast agents, particularly superparamagnetic iron oxide nanoparticles, face issues with toxicity, stability, and specificity in targeting antigen presenting cells, leading to suboptimal diagnostic capabilities for conditions like cancer and sepsis.

Innovation Solution

A superparamagnetic MRI contrast agent coated with carboxylated mannan is developed, which enhances in vivo stability and biocompatibility, allowing specific targeting and visualization of antigen presenting cells through the introduction of a carboxyl group into mannan, improving the agent's ability to be introduced into these cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If pure superparamagnetic iron oxide particles are used as MRI contrast agents, then high sensitivity and μM level imaging capability are achieved, but toxicity increases and in vivo stability decreases

Engineering Contradiction:
Improveimaging sensitivityVSAvoidtoxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

Mannan acts as an intermediary coating material between the superparamagnetic iron oxide particles and the biological environment. The mannan coating provides a biocompatible interface that reduces direct contact between toxic iron oxide and biological tissues, while maintaining the magnetic properties needed for high-sensitivity imaging at μM levels.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The contrast agent is formulated as a composite material combining superparamagnetic iron oxide particles with mannan coating. This composite structure integrates the high magnetic sensitivity of iron oxide with the biocompatibility and stability of mannan, simultaneously achieving both imaging sensitivity and reduced toxicity.

Inventive Principle:
Principle #40Composite materials

2Volume of moving object

If pure superparamagnetic iron oxide particles are used, then high volume-to-surface area ratio is achieved, but hydrophobic interaction and coagulation increase forming clusters

Engineering Contradiction:
Improveparticle volumeVSAvoidcolloidal stability
Core Design Contradiction:
Volume of moving objectVSStability of the object's composition

Solution Approach 1:

Mannan serves as a stabilizing intermediary layer on the particle surface that prevents direct hydrophobic interactions between iron oxide particles. This coating layer provides steric stabilization that maintains colloidal stability and prevents coagulation and clustering, allowing the particles to remain dispersed in physiological environments.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If conventional coating materials like dextran or synthetic polymers are used, then stability is improved, but specificity in targeting antigen presenting cells is reduced

Engineering Contradiction:
Improvein vivo stabilityVSAvoidtargeting specificity
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The mannan coating provides localized functional properties that differ from conventional coatings. Specifically, mannan contains mannose residues that can interact with mannose receptors on antigen-presenting cells, providing localized targeting functionality at the particle surface while maintaining overall colloidal stability in circulation.

Inventive Principle:
Principle #3Local quality

4Adaptability or versatility

If mannan is used for coating, then targeting ability is improved, but biotoxicity and circulation trapping increase

Engineering Contradiction:
Improvetargeting abilityVSAvoidbiotoxicity
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The physical and chemical parameters of the mannan coating are optimized to balance targeting ability with reduced toxicity. By controlling the degree of carboxymethylation and molecular weight of mannan, the coating maintains sufficient mannose residues for receptor targeting while modifying the overall surface chemistry to reduce biotoxicity and improve circulation half-life.

Inventive Principle:
Principle #35Parameter changes

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 carboxylated mannan-coated superparamagnetic nanoparticles demonstrate improved stability, reduced toxicity, and enhanced contrast-enhancement ability for antigen presenting cells, facilitating early diagnosis of cancer metastasis and sepsis with improved spatial resolution and reduced radiation risk compared to conventional methods.

Implementation Method 1

The pure superparamagnetic iron oxide particle (1) is hydrophobic and shows the high ratio of volume to surface area, suggesting the strong hydrophobic interaction and coagulation that can form a cluster easily

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

The pure superparamagnetic iron oxide particle (1) is hydrophobic and shows the high ratio of volume to surface area, suggesting the strong hydrophobic interaction and coagulation that can form a cluster easily

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 3

MRI contrast agents are divided into two groups: paramagnetic contrast agents and superparamagnetic contrast agents. The superparamagnetic contrast agent widely used in clinical is prepared by using superparamagnetic nanoparticles represented by such superparamagnetic iron oxide (SPIO) as magnetite (Fe3O4) and maghemite (Fe2O3). These agents alter the T1 and T2 relaxation times of tissues and body cavities where they are present

Methodology Applied
Scientific EffectSuperparamagnetism: Superparamagnetism

Data Source

PatentUS8961935B2MRI contrast agent coated with carboxylated mannan and method for producing the same
Publication Date: 2015.02.24 INTRON BIOTECHNOLOGY INC
  • US8961935B2 patent drawing
  • US8961935B2 patent drawing
  • US8961935B2 patent drawing

AI summary

The present invention relates to a magnetic resonance imaging (MRI) contrast agent coated with carboxylated mannan, particularly a carboxylated mannan coated superparamagnetic MRI contrast agent specifically targeting antigen presenting cells and having excellent in vivo stability, and a method for producing the same. The MRI contrast agent coated with carboxylated mannan of the present invention can provide excellent in vivo stability and biocompatibility owing to its high surface negative charge, and can be introduced specifically into antigen presenting cells owing to mannose of mannan, so as to visualize the antigen presenting cells and the tissue containing the antigen presenting cells in MRI.