MnCaP Polymer Nanoparticle Composite for MRI Contrast

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Solution Overview

Problem

Current MRI contrast agents lack site specificity, leading to difficulties in accurately diagnosing tumors due to rapid diffusion and potential side effects, and there is a need for agents that can selectively accumulate at tumor tissues with high contrast and minimal side effects.

Innovation Solution

A polymer nanoparticle composite incorporating MnCaP, formed by the reaction of HPO42- with Ca2+ and Mn2+, which uses a block copolymer with a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment, allowing Mn2+ ion release in low pH environments for enhanced MRI contrast.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If Gd-DTPA is used as an MRI contrast agent, then contrast enhancement is achieved, but site specificity is lost and rapid diffusion occurs

Engineering Contradiction:
Improvetumor detection accuracyVSAvoidnephrogenic systemic fibrosis risk
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent segments the contrast agent into two functional parts: a Gd-DTPA complex for contrast enhancement and a nanoparticle carrier for targeted delivery. The Gd-DTPA is encapsulated within polymer nanoparticles, separating the contrast function from the delivery function, enabling targeted accumulation at tumor sites while reducing systemic exposure and kidney-related side effects

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The polymer nanoparticle acts as an intermediary carrier that transports Gd-DTPA to the target tissue. The nanoparticle surface is functionalized with targeting moieties that mediate specific binding to tumor cells, allowing the contrast agent to reach the destination without directly interacting with healthy kidney tissue, thus reducing nephrogenic systemic fibrosis risk

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If Mn ion is administered alone at high concentration, then MRI contrast is enhanced, but cardiac toxicity occurs

Engineering Contradiction:
ImproveMRI contrastVSAvoidcardiac toxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent creates a composite material combining Mn ions with polymer nanoparticle carriers. The Mn ions are incorporated into the nanoparticle structure, forming a composite that provides MRI contrast enhancement while the nanoparticle matrix controls Mn ion release and distribution, preventing the high local concentrations that cause cardiac toxicity

Inventive Principle:
Principle #40Composite materials

3Measurement precision

If conventional MRI contrast agents are used, then tumor visualization is possible, but small tumors cannot be identified due to signal burial

Engineering Contradiction:
Improvetumor detection capabilityVSAvoidsmall tumor detection
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent changes the physical parameters of the contrast agent by formulating it as nanoparticles with controlled size distribution (20-200 nm). This size parameter optimization enables the contrast agent to accumulate in small tumors through enhanced permeability and retention effect, generating sufficient signal intensity even in microcarcinomas that were previously undetectable

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If fluorescent probes are used for smart imaging, then cancer property depiction is achieved, but MRI contrast capability is limited

Engineering Contradiction:
Improvecancer property assessmentVSAvoidMRI contrast
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent creates a multi-functional nanoparticle system that combines MRI contrast capability with smart response functions. The nanoparticle incorporates both Mn or Gd-DTPA for MRI contrast and pH-responsive components that enable smart imaging of cancer properties. This universal platform achieves both MRI contrast and adaptive cancer characterization in a single agent

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 polymer nanoparticle composite selectively accumulates at tumor tissues, providing high contrast with reduced side effects and prolonged imaging capabilities, enabling accurate detection of tumors and assessment of malignancy, including microcarcinomas and metastatic tumors.

Implementation Method 1

MnCaP that is producible by the reaction of HPO42- with Ca2+ and Mn2+ and has a solubility product constant (Ksp) of 10-11.3 or less, wherein the block copolymer comprises a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment

Methodology Applied
Scientific EffectpH-responsive ion release:

Implementation Method 2

A polymer nanoparticle composite incorporating a substance that has MRI contrast ability (MRI imaging ability)

Methodology Applied
Scientific EffectMRI contrast enhancement:

Data Source

PatentEP3037107B1Polymer nanoparticle composite and composition for MRI imaging including same
Publication Date: 2019.10.09 THE UNIV OF TOKYO
  • EP3037107B1 patent drawingFigure 1
  • EP3037107B1 patent drawingFigure 2
  • EP3037107B1 patent drawingFigure 3

AI summary

The present invention provides a safe polymer nanoparticle composite with few side effects, and an MRI contrast agent incorporating said polymer nanoparticle composite. The polymer nanoparticle composite is capable of specifically accumulating on a tumor tissue to selectively extract the tissue, exhibiting high contrast even when used in small amounts, and enabling imaging over prolonged periods of time. This polymer nanoparticle composite is characterized by containing a block copolymer that includes a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment, and MnCaP.