Peptide Hydrogel CEST Contrast Agents for Safe Multi-Color MRI

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Solution Overview

Problem

Current magnetic resonance (MR) contrast agents, particularly those containing paramagnetic metals, pose safety concerns due to toxicity and limited ability to provide multi-color contrast, necessitating the development of non-metallic, biodegradable compounds for safe and efficient multi-modal imaging.

Innovation Solution

A peptide-based hydrogel CEST agent is developed, incorporating lysine, arginine, serine, threonine, histidine, tryptophan, and unnatural amino acids with heterocyclic protons, capable of producing chemical shifts and exchange rates suitable for generating CEST contrast in MR imaging, allowing for safe and simultaneous tracking of multiple entities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If paramagnetic metal-based contrast agents are used, then strong signal enhancement is achieved, but toxicity and safety concerns arise

Engineering Contradiction:
Improvesignal enhancement capabilityVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful paramagnetic metal components from contrast agents, replacing them with non-metallic diamagnetic compounds that maintain CEST contrast capabilities without the associated toxicity concerns

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs biodegradable peptide-based hydrogels as temporary, disposable contrast agents that safely degrade in the body after serving their imaging function, eliminating long-term metal accumulation risks

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If paramagnetic metal-based contrast agents are used, then one type of contrast is provided, but multi-color detection capability is lost

Engineering Contradiction:
Improvecontrast capabilityVSAvoidmulti-color detection capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent designs peptide-based CEST agents with multiple exchangeable proton pools at different chemical shifts, enabling a single agent to provide multi-color detection capabilities for simultaneously tracking multiple biological processes or agents

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

Solution Approach 2:

The patent utilizes variations in chemical shift parameters of exchangeable protons to create distinct CEST contrast signatures, allowing differentiation and simultaneous detection of multiple targets through frequency-specific saturation transfer

Inventive Principle:
Principle #35Parameter changes

3Reliability

If high doses of contrast agents are administered, then signal enhancement is improved, but safety risks increase

Engineering Contradiction:
Improvesignal enhancementVSAvoidsafety risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent exploits the high sensitivity of CEST agents, which can detect micromolar concentrations of polypeptide gene carriers and close to nanomolar concentrations of polynucleotides, allowing effective imaging at very low doses that minimize safety risks

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 peptide-based hydrogel provides effective, biocompatible CEST contrast for MR imaging, overcoming toxicity issues and enabling multi-color detection, thereby enhancing imaging capabilities and safety by using non-metallic, biodegradable compounds.

Implementation Method 1

A peptide-based hydrogel CEST agent is developed, incorporating lysine, arginine, serine, threonine, histidine, tryptophan, and unnatural amino acids with heterocyclic protons, capable of producing chemical shifts and exchange rates suitable for generating CEST contrast in MR imaging

Methodology Applied
Scientific EffectChemical Exchange Saturation Transfer (CEST):

Data Source

PatentUS11235075B2Peptide hydrogels generating chemical exchange saturation transfer MRI contrast and uses thereof
Publication Date: 2022.02.01 KRIEGER KENNEDY INSTITUTE INC

AI summary

The present invention provides novel hydrogels through peptides, which are designed to self-assemble and produce magnetic resonance (MR) contrast through chemical exchange saturation transfer (CEST). The location and integrity of these gels could consequently be tracked using MR imaging. The self-assembly of the peptides into hydrogels can be brought about by a change in pH, ionic strength, temperature, and concentration of ions.