Prefunctionalized Gold Nanoparticles with Dithiophosphate Anchors

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Solution Overview

Problem

The high modularity of functionalized gold nanoparticles leads to controversies regarding delivery mechanisms, cell penetration, and efficacy, due to varying manufacturing methods and parameters, resulting in instability and limited storage stability, which complicates their biomedical applications.

Innovation Solution

The development of prefunctionalized metallic nanoparticles with a thiol-reactive surface prefunctionalized by a bifunctional molecule containing dithiophosphate groups and a short further-functionalization stub, allowing for standardized biofunctionalization and storage stability, enabling easy and reproducible attachment of desired biomolecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If gold nanoparticles are functionalized with various derivatized compositions to achieve high modularity and adaptability for biomedical applications, then the versatility and customization capability are improved, but the manufacturing consistency and storage stability deteriorate due to different manufacturing methods and parameters

Engineering Contradiction:
Improvefunctionalization versatilityVSAvoidstorage stability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-functionalizing gold nanoparticles with a standardized oligonucleotide layer during manufacturing. This pre-functionalization creates a stable base layer that ensures consistent storage stability while maintaining the ability to perform additional user-specific functionalization later. The standardized oligonucleotide layer is attached in advance to create reproducible building blocks that can be stored and then customized as needed.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the functionalization process into two distinct stages: a standardized pre-functionalization step performed during manufacturing that ensures storage stability, and a user-specific further-functionalization step that provides customization. This segmentation allows the base nanoparticle to have consistent, reproducible properties while still enabling diverse applications through additional functionalization by the user.

Inventive Principle:
Principle #1Segmentation

2Stability of the object's composition

If proteins such as BSA are added to coat nanoparticles to prevent agglomeration in cell culture medium, then the storage stability and dispersion are improved, but the selective chemical derivatization capability deteriorates due to the protein coating blocking access to the particle surface

Engineering Contradiction:
Improvedispersion stabilityVSAvoidderivatization capability
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent uses an oligonucleotide layer as an intermediary between the gold nanoparticle surface and the external environment. This oligonucleotide layer provides steric stabilization to prevent agglomeration in cell culture medium, similar to protein coatings, but crucially leaves the gold surface accessible for selective chemical derivatization. The oligonucleotide acts as a mediator that simultaneously provides stability and maintains reactivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If various research groups use their own compositions of derivatized gold nanoparticles with different manufacturing methods, then the customization and specific application optimization are improved, but the comparability of results and reproducibility deteriorate

Engineering Contradiction:
Improveapplication optimizationVSAvoidresult comparability
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent creates a universal standardized oligonucleotide-functionalized gold nanoparticle platform that can serve multiple different applications. The standardized pre-functionalization provides a common base that ensures reproducibility and comparability across different studies, while the user-specific further-functionalization capability allows optimization for specific applications. This universal platform enables different research groups to work with the same standardized building blocks.

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

4Ease of operation

If the biofunctionalization process is performed in a single step to simplify the procedure, then the ease of operation is improved, but the ability to maintain confidentiality and control over the functionalization process deteriorates

Engineering Contradiction:
Improvefunctionalization simplicityVSAvoidprocess confidentiality
Core Design Contradiction:
Ease of operationVSLoss of information

Solution Approach 1:

The patent segments the functionalization process into two stages: a standardized pre-functionalization step that can be performed and controlled by the manufacturer, and a user-specific further-functionalization step that the end user performs. This segmentation allows the manufacturer to maintain confidentiality over the specific functionalization details while providing a simple, standardized base product. The user then performs the final customization step in their own controlled environment.

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

This approach provides stable, reproducible, and easily customizable biofunctionalized nanoparticles with enhanced storage stability, allowing for efficient biofunctionalization in two sub-steps, prefunctionalization and user-specific further-functionalization, ensuring high comparability of results and maintaining confidentiality of biofunctionalization processes.

Implementation Method 1

the anchor component comprises one or more dithiophosphate groups

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

thiol-reactive metallic nanoparticle that is prefunctionalized by a bifunctional molecule

Methodology Applied
Scientific EffectChemisorption: Chemisorption

Data Source

PatentUS11224664B2Functionalized metal nanoparticle
Publication Date: 2022.01.18 FRIZ BIOCHEM FUR BIOANALYTIK MBH
  • US11224664B2 patent drawing
  • US11224664B2 patent drawing
  • US11224664B2 patent drawing

AI summary

The present invention relates to a prefunctionalized metallic nanoparticle (10) as a standardized basic building block of biofunctionalized nanoparticles (40), having a thiol-reactive metallic nanoparticle (12) that is prefunctionalized by a bifunctional molecule (20) that consists of an anchor component (22) and a short further-functionalization stub (24). Here, it is provided that the anchor component (22) comprises one or more dithiophosphate groups, and the short further-functionalization stub (24) is adapted for the attachment of a desired biofunctionalization (30) and is selected from the group consisting ofi) an unmodified standardized oligonucleotide strand (26) having 2 to 18 bases for further-functionalization with biomolecules (30) having a terminal complementary strand (36) of the standardized oligonucleotide strand (26), andii) a 2- to 18-base-long oligonucleotide strand (50; 60) that is modified with a terminal reactive group (52; 62) for biomolecules.