Antimicrobial Nanoparticles via Catechol-Metal Coordination

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Solution Overview

Problem

Current antimicrobial agents face challenges such as increased resistance, toxicity, and limited effectiveness against intracellular bacteria, as well as difficulties in adhering to various surfaces, particularly wet surfaces, and maintaining antimicrobial properties across a wide pH range.

Innovation Solution

Development of antimicrobial nanoparticles with inherent antimicrobial activity, comprising an antibiotic peptide linked to a mussel adhesive protein derivative modified with a catechol derivative and a coordinatable metal, which can adhere to surfaces and maintain activity from pH 0.1 to 6.5, allowing for effective intracellular infection prevention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antimicrobial agents are used, then antimicrobial activity is achieved, but resistance to antimicrobial agents increases and effectiveness against intracellular bacteria is limited

Engineering Contradiction:
Improveantimicrobial effectivenessVSAvoidbacterial resistance
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention combines antibiotic peptides with mussel adhesive protein derivatives to create composite antimicrobial nanoparticles. This composite structure integrates the antimicrobial function of peptides with the adhesion capability of mussel proteins, enabling the material to penetrate cells and kill intracellular bacteria while avoiding resistance development through multiple action mechanisms

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention modifies the mussel adhesive protein by changing the chemical state of tyrosine residues to catechol derivatives through chemical modification. This parameter change enables metal coordination and enhances both adhesion to wet surfaces and stability across broad pH ranges (0.1-6.5), while the nanoparticle formulation changes the delivery parameters to enable intracellular penetration

Inventive Principle:
Principle #35Parameter changes

2Strength

If chemical synthetic adhesives are used, then adhesion to surfaces is achieved, but adhesion to wet surfaces and flexibility are insufficient

Engineering Contradiction:
Improveadhesive strengthVSAvoidadhesion to wet surfaces
Core Design Contradiction:
StrengthVSAdaptability or versatility

Solution Approach 1:

The catechol derivative groups in the mussel adhesive protein derivative act as intermediaries that form coordination bonds with metal ions. This intermediary mechanism enables strong adhesion to wet surfaces and various substrates by creating stable metal-catechol complexes that bridge the adhesive and the surface, overcoming the limitations of conventional chemical adhesives

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite adhesive system combining mussel adhesive protein derivatives with metal ions. This composite material integrates the biological adhesion mechanism of mussel proteins with the coordination chemistry of metal-catechol interactions, achieving superior adhesion strength and flexibility compared to pure chemical adhesives

Inventive Principle:
Principle #40Composite materials

3Strength

If naturally extracted mussel adhesive proteins are used, then excellent adhesion properties are achieved, but production cost and scalability are limited

Engineering Contradiction:
Improveadhesive propertyVSAvoidproduction scalability
Core Design Contradiction:
StrengthVSEase of manufacture

Solution Approach 1:

The invention creates a simplified copy of the natural mussel adhesive protein function by using genetically engineered variants with standardized catechol derivative modifications. This copied version maintains the essential adhesion properties while enabling scalable production through recombinant DNA technology, eliminating the need to process large numbers of natural mussels

Inventive Principle:
Principle #26Copying

4Stability of the object's composition

If nanoparticles carrying antimicrobial agents are used, then stability of antimicrobial agents is improved, but inherent antimicrobial activity of the nanoparticle material itself is absent

Engineering Contradiction:
Improveantimicrobial agent stabilityVSAvoidinherent antimicrobial activity
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The invention merges the antimicrobial agent (antibiotic peptide) with the nanoparticle material (mussel adhesive protein derivative) into a single integrated structure. The peptide is covalently linked to the mussel protein, creating a nanoparticle that possesses both the stability of the protein carrier and the inherent antimicrobial activity of the peptide, eliminating the need for separate loading processes

Inventive Principle:
Principle #5Merging (Combining)

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 exhibit stable antimicrobial activity across a broad pH range, effectively inhibiting bacterial growth and killing infected bacteria within cells without harming host cells, while also providing excellent adhesion properties to various surfaces.

Implementation Method 1

a metal capable of coordinating with the mussel adhesive protein derivative

Methodology Applied
Scientific EffectCoordination:

Implementation Method 2

the antibiotic peptides break down or puncture bacterial cell membranes, resulting in loss of intracellular materials

Methodology Applied
Scientific EffectMembrane disruption:

Implementation Method 3

nanoparticles, capable of invading animal cells through a phagocytosis or pinocytosis pathway

Methodology Applied
Scientific EffectPhagocytosis:

Implementation Method 4

nanoparticles, capable of invading animal cells through a phagocytosis or pinocytosis pathway

Methodology Applied
Scientific EffectPinocytosis:

Data Source

PatentEP3656785B1Antimicrobial adhesive protein, antimicrobial nanoparticle, antimicrobial composition comprising same nanoparticle, and preparation method for same composition
Publication Date: 2024.09.11 POHANG IRON & STEEL CO LTD
  • EP3656785B1 patent drawingFigure 1~2
  • EP3656785B1 patent drawingFigure 3~4
  • EP3656785B1 patent drawingFigure 5~6

AI summary

The present invention relates to an antimicrobial adhesive protein, an antimicrobial nanoparticle, an antimicrobial composition comprising the same nanoparticle, and a preparation method for the same composition and, more particularly, to an antimicrobial adhesive protein in which an antibiotic peptide is linked to a mussel adhesive protein, a mussel adhesive protein derivative in which a tyrosine residue within the antimicrobial adhesive protein is modified with a catechol derivative, an antimicrobial nanoparticle including a metal capable of forming a coordinate bond with a derivative of the mussel adhesive protein and having intrinsic antimicrobial activity, an antimicrobial composition comprising the same nanoparticle, and a preparation method for the same composition.