Gd(III)-Dithiolane Gold Nanoparticle Conjugates for MRI

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Solution Overview

Problem

Current gold nanoparticle conjugates for biological and medical applications face limitations in in vivo tracking, requiring animal sacrifice and lacking temporal resolution due to challenges in imaging gold nanoparticles within living subjects.

Innovation Solution

Development of Gd(III)-dithiolane gold nanoparticle conjugates that allow for facile functionalization and accumulation in pancreatic tissue, enabling magnetic resonance imaging (MRI) without the need for additional chemical reagents, and providing improved spatial and temporal resolution for tracking gold nanoparticles in vivo.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If traditional gold nanoparticle conjugates are used for in vivo tracking, then the particles can be delivered to target tissues, but temporal resolution is lost due to requiring animal sacrifice for tracking

Engineering Contradiction:
Improvetemporal resolutionVSAvoidtracking capability
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The patent combines gold nanoparticles with Gd(III) contrast agents into a single conjugate system. The gold nanoparticle provides the therapeutic/delivery function while the Gd(III) agent provides MRI contrast, allowing both tracking and delivery functions to be performed simultaneously in living subjects without sacrifice.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The gold nanoparticle conjugate system performs multiple functions: it serves as a therapeutic delivery vehicle, an MRI contrast agent for tracking, and a targeted delivery system. This multi-functionality eliminates the need for separate tracking methods that would require animal sacrifice.

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

2Quantity of substance

If additional chemical reagents are used for functionalization of gold nanoparticles, then contrast agent loading can be increased, but the conjugation process becomes more complex

Engineering Contradiction:
Improvecontrast agent loadingVSAvoidconjugation process complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The dithiolane-modified Gd(III) contrast agent self-assembles onto the gold nanoparticle surface through spontaneous gold-thiol bond formation. This self-service mechanism eliminates the need for additional chemical reagents, reducing agents, or complex multi-step conjugation protocols, while achieving high contrast agent loading.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The dithiolane group acts as an intermediary that facilitates the connection between the Gd(III) contrast agent and the gold nanoparticle surface. This intermediary enables direct conjugation without requiring additional chemical reagents or complex activation steps.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If conventional conjugation strategies are used, then gold nanoparticles can be functionalized, but the process requires reducing agents and extended salt aging time

Engineering Contradiction:
Improveconjugation easeVSAvoidconjugation time
Core Design Contradiction:
Ease of manufactureVSLoss of time

Solution Approach 1:

The dithiolane-modified Gd(III) contrast agent spontaneously conjugates to the gold nanoparticle surface through direct gold-thiol bond formation without requiring reducing agents or extended salt aging. This self-service mechanism dramatically simplifies the manufacturing process and reduces conjugation time from days to hours or minutes.

Inventive Principle:
Principle #25Self-service

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

Enables non-invasive longitudinal studies of pancreatic tissue progression and cell tracking with enhanced Gd(III) loading and stability, allowing for effective MRI contrast enhancement and improved cellular uptake without animal sacrifice.

Implementation Method 1

tracking the particles in vivo generally require sacrifice of the subject, which results in a loss of temporal resolution. This allows users (e.g., researchers, clinicians, etc.) to, for example, take advantage of MRI's excellent spatial and temporal resolution for tracking gold nanoparticles.

Methodology Applied
Scientific EffectMagnetic resonance imaging (MRI):

Implementation Method 2

dithiolane-modified Gd(lll) contrast agents are functionalized onto gold nanoparticle surfaces through gold-thiol bond formation.

Methodology Applied
Scientific EffectGold-thiol bond formation: Chemical Bonding

Data Source

PatentUS10786582B2Gd(III)-dithiolane gold nanoparticle conjugates
Publication Date: 2020.09.29 NORTHWESTERN UNIV
  • US10786582B2 patent drawing
  • US10786582B2 patent drawing
  • US10786582B2 patent drawing

AI summary

Provided herein are compositions Gd(III)-dithiolane gold nanoparticle conjugates and methods of use thereof. In particular, compositions and method find use in in vivo imaging (e.g., magnetic resonance imaging (MRI)), for example, of pancreatic tissue.