Biodegradable SHG Nanoprobe with Polymer Shell

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Solution Overview

Problem

Current second-harmonic generation (SHG) probes made of inorganic materials are not biodegradable, limiting their clinical use, and biocompatible SHG probes prepared from oligopeptides tend to aggregate in aqueous solutions, making them unsuitable for biological applications.

Innovation Solution

Development of biodegradable, biocompatible, water-soluble nanoparticles with a shell layer of biodegradable polymer encapsulating structured oligopeptides that generate a second-harmonic light signal upon illumination, preventing aggregation and maintaining stability in aqueous solutions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If inorganic materials are used for SHG probes, then SHG signal generation is achieved, but biodegradability is lost

Engineering Contradiction:
ImproveSHG signal generationVSAvoidbiodegradability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses composite materials by combining inorganic SHG-generating cores (barium titanate nanoparticles) with organic biodegradable polymer shells (PLA, PLGA, or PCL). This composite structure allows the nanoprobe to maintain SHG signal generation from the inorganic core while gaining biodegradability and biocompatibility from the organic shell, enabling clinical application.

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If oligopeptides are used for biocompatible SHG probes, then biocompatibility is achieved, but aggregation in aqueous solutions occurs

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidaggregation resistance
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent introduces biodegradable polymers (PLA, PLGA, PCL) as intermediary materials that bridge the gap between oligopeptides and aqueous biological environments. These polymers form stable shells around the peptide structures, preventing direct interaction between hydrophobic peptide aggregates and water, thereby maintaining colloidal stability and preventing aggregation while preserving biocompatibility.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The biodegradable polymer forms a flexible shell around the oligopeptide core structure. This shell provides steric stabilization and prevents aggregation of the nanoparticles in aqueous solutions by creating a hydrophilic interface with the surrounding water environment, while allowing the internal oligopeptide structure to maintain its SHG-generating conformation.

Inventive Principle:
Principle #30Flexible shells and thin films

3Reliability

If peptides self-assemble in organic solvents, then SHG structures are formed, but water-suspensability is lost

Engineering Contradiction:
ImproveSHG structure formationVSAvoidwater-suspensability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the nanoprobe into distinct functional modules: an organic solvent-based core where peptides self-assemble into SHG-generating structures, and a separate biodegradable polymer shell that provides water-suspensability. This segmentation allows the core to maintain its SHG functionality formed in organic solvents while the shell enables dispersion and stability in aqueous biological environments.

Inventive Principle:
Principle #1Segmentation

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 provide a stable, high-intensity SHG signal suitable for imaging applications, remaining non-aggregated and functional under varying environmental conditions, enabling precise targeting and imaging in biomedical applications.

Implementation Method 1

SHG is a nonlinear optical scattering-process, in which due to a non-linear susceptibility term of the scattering material, two photons with the same frequency result in a single, new photon with twice the energy, and therefore twice the frequency of the two initial photons.

Methodology Applied
Scientific EffectSecond-harmonic generation: Second Harmonic Generation

Data Source

PatentEP3518986B1Biodegradable, second-harmonic-generating nanoprobe for biomedical imaging applications
Publication Date: 2021.12.15 MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN EV
  • EP3518986B1 patent drawingFigure 1~2
  • EP3518986B1 patent drawingFigure 3~4D
  • EP3518986B1 patent drawingFigure 5~6D

AI summary

The present invention refers to Biodegradable, biocompatible, water-suspensable nanoparticle (1), for generating a second- or third-harmonic light signal upon illumination, as well as a method for preparing an aqueous suspension comprising said nanoparticle, a method for second-harmonic generation imaging of the nanoparticle (1) as and a use of the nanoparticle (1) for second-harmonic generation imaging. The nanoparticle (1) according to the invention comprises - a shell layer (2) comprising a biodegradable polymer (3), wherein the shell layer (2) encloses - a plurality (40) of oligopeptides (4), wherein the plurality (40) of oligopeptides (4) is structured such that a second-harmonic light signal is generated upon illumination of the nanoparticle (1) with light.