Aptamer-Conjugated USPIO for Specific Atherosclerosis Plaque Imaging

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Solution Overview

Problem

Current MRI diagnostic technologies for atherosclerosis face challenges in achieving high resolution and specificity due to non-targeted distribution of ultra-small superparamagnetic iron oxide (USPIO) particles, which are mainly taken up by the reticuloendothelial system rather than specifically targeting atherosclerotic plaques.

Innovation Solution

A targeting aptamer for atherosclerosis is developed using the SELEX method to specifically bind macrophage-derived foam cells, combined with silane-coated ferriferrous oxide nanoparticles to create a targeted MRI nano-contrast agent that enhances the specificity and accuracy of plaque detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If USPIO particles are used as MRI contrast agents for atherosclerosis imaging, then the imaging capability for blood vessels is improved, but the specificity for targeting atherosclerotic plaques deteriorates because USPIO particles are mainly taken up by the reticuloendothelial system rather than specifically targeting plaques

Engineering Contradiction:
Improveimaging capabilityVSAvoidspecificity for plaque targeting
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces aptamers as intermediary molecules that specifically bind to VCAM-1 on activated endothelial cells in atherosclerotic plaques. These aptamers serve as mediators between the USPIO particles and the target plaques, enabling specific targeting while maintaining the imaging capabilities of USPIO. The aptamer-USPIO conjugate system allows the contrast agent to accumulate specifically at plaque sites rather than being randomly distributed by the reticuloendothelial system.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If conventional MRI techniques are used for coronary artery imaging, then the noninvasive diagnostic capability is maintained, but the spatial resolution deteriorates due to the small diameter and bent direction of coronary arteries

Engineering Contradiction:
Improvenoninvasive diagnostic capabilityVSAvoidspatial resolution
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent applies local quality by creating contrast agents with specific biological targeting properties that concentrate imaging signal precisely at the plaque locations within the coronary arteries. The aptamer-USPIO conjugates exhibit localized accumulation at VCAM-1 expressing sites, providing high spatial resolution images of specific pathological regions without requiring invasive procedures or complex scanning protocols.

Inventive Principle:
Principle #3Local quality

3Manufacturing precision

If MRI scanning time is extended to improve spatial resolution for coronary arteries, then the imaging detail is improved, but the time required for examination increases which is problematic given the effects of respiration and heart rate

Engineering Contradiction:
Improvespatial resolutionVSAvoidexamination time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent employs preliminary action by pre-targeting the atherosclerotic plaques with aptamer-USPIO conjugates before MRI scanning. This pre-targeting allows the contrast agent to accumulate at the plaque sites in advance, so that when the MRI scan is performed, high-resolution images are obtained quickly without requiring prolonged scanning times. The biological targeting process occurs prior to imaging, decoupling the resolution achievement from scan duration.

Inventive Principle:
Principle #10Preliminary action

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 targeting aptamer significantly improves the specificity of the MRI nano-contrast agent, allowing for high-resolution imaging of atherosclerotic plaques with increased target-to-nontarget ratios, enabling early and specific diagnosis of atherosclerosis with improved spatial and temporal resolution.

Implementation Method 1

Ultra-small superparamagnetic iron oxide (USPIO) is constituted by a single crystal core consisting of Fe 3 O 4 or Fe 2 O 3 and an outer layer coating. After entering into an applied magnetic field, USPIO particles are distributed unevenly, which makes a non-uniform local magnetic field, generates a magnetizing effect, thus accelerates T 2 relaxation of proton dephasing

Methodology Applied
Scientific EffectSuperparamagnetism: Superparamagnetism

Implementation Method 2

After entering into an applied magnetic field, USPIO particles are distributed unevenly, which makes a non-uniform local magnetic field

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 3

the targeting aptamer for atherosclerosis is a targeting aptamer fragment for atherosclerosis obtained through screening of macrophage-derived foam cells together with reverse screening of smooth muscle cells, endothelial cells, and THP-1 cells using a SELEX method

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentEP3009512B1Targeting aptamer for atherosclerosis and preparation method and application thereof
Publication Date: 2020.05.13 GUANGZHOU TONGPENG ZHONGXU PHARMA
  • EP3009512B1 patent drawingFigure 1~3
  • EP3009512B1 patent drawingFigure 4~6
  • EP3009512B1 patent drawingFigure 7~10

AI summary

Disclosed are a targeting aptamer for atherosclerosis and a preparation method and application thereof. The targeting aptamer is a targeting aptamer fragment for atherosclerosis obtained through screening of macrophage-derived foam cells together with reverse screening of smooth muscle cells, endothelial cells, and THP-1 cells using a SELEX method; and the use of the targeting aptamer in preparation of an MRI targeting nano-contrast agent for atherosclerosis allows the specific binding of the MRI targeting nano-contrast agent for atherosclerosis only with the macrophage-derived foam cells, and allows high specific binding thereof with vascular tissues with AS lesion, thus improving targeting effect of the MRI targeting nano-contrast agent for atherosclerosis and realizing early specific diagnosis of arterial sclerosis.