Liver-Targeted Dual-Modal Probe for Hepatic Inflammation Detection

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Solution Overview

Problem

Current methods for diagnosing early hepatic inflammation are inadequate due to the difficulty in detecting reactive oxygen species (O2·−) in real-time, leading to missed diagnoses and a need for more accurate and sensitive imaging strategies.

Innovation Solution

A liver-targeted fluorescent/photoacoustic dual-modal probe (hCy-Tf-CA) is developed, which utilizes a hemi-cyanine fluorophore and cholic acid for active targeting and enhanced sensitivity to O2·−, allowing for precise in situ visualization of hepatic inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If single NIR fluorescence imaging is used for detecting hepatic inflammation, then imaging sensitivity is improved, but tissue penetration ability and spatial resolution deteriorate

Engineering Contradiction:
Improveimaging sensitivityVSAvoidtissue penetration depth
Core Design Contradiction:
Measurement precisionVSLength of stationary object

Solution Approach 1:

The patent combines fluorescence imaging and photoacoustic imaging into a dual-modal probe system. The probe contains both a fluorophore component for fluorescence imaging and a photoacoustic agent component for photoacoustic imaging, allowing simultaneous acquisition of both modalities to achieve both high sensitivity and deep tissue penetration

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The dual-modal probe serves multiple imaging functions simultaneously - it provides both fluorescence signaling for high sensitivity detection and photoacoustic signaling for deep tissue penetration and spatial resolution, making a single probe perform the roles of two separate imaging systems

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

2Adaptability or versatility

If small molecule dual-modal probes are used for in vivo bioimaging, then imaging modality integration is improved, but signal-to-background ratio and biodistribution predictability deteriorate

Engineering Contradiction:
Improveimaging modality integrationVSAvoidsignal-to-background ratio
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The probe incorporates a liver-targeting moiety that confers selective accumulation properties in the liver tissue. This local targeting capability ensures the probe concentrates in the region of interest (liver), improving the signal-to-background ratio by reducing off-target signals and enhancing the specificity of the imaging measurement

Inventive Principle:
Principle #3Local quality

3Measurement precision

If high dose probes are administered to enhance signal-to-background ratio, then imaging sensitivity is improved, but metabolic stress and toxicity deteriorate

Engineering Contradiction:
Improvesignal-to-background ratioVSAvoidmetabolic stress
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The liver-targeting moiety on the probe enables selective accumulation in the liver, allowing effective imaging at lower doses by concentrating the probe signal where needed. This reduces the total dose required compared to non-targeted probes, thereby minimizing metabolic stress and toxicity while maintaining adequate signal-to-background ratio

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The probe's targeting moiety automatically directs the probe to the liver tissue through passive accumulation mechanisms, eliminating the need for high doses to overcome poor biodistribution. The probe self-concentrates in the target organ, improving imaging quality at lower administered doses and reducing metabolic burden

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

The probe significantly increases fluorescence intensity upon reacting with O2·−, providing high selectivity and sensitivity for early hepatic inflammation detection, with good chemical stability and biocompatibility, enabling non-invasive real-time monitoring of O2·− fluctuations.

Implementation Method 1

a hemi-cyanine fluorophore based probe for accurately detecting endogenous O2·−

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

photoacoustic (PA) imaging combines the imageological superiorities of fluorescence and ultrasound imaging

Methodology Applied
Scientific EffectPhotoacoustic effect: Photoacoustic Effect

Data Source

PatentUS20240165272A1Liver-targeted fluorescence/photoacoustic dual-modal probe for early detecting drug-induced hepatic inflammation and autoimmune hepatitis
Publication Date: 2024.05.23 BEIJING UNIV OF TECH
  • US20240165272A1 patent drawing
  • US20240165272A1 patent drawing
  • US20240165272A1 patent drawing

AI summary

A liver-targeted fluorescence/photoacoustic dual-modal probe for the early detection of drug-induced hepatic inflammation and autoimmune hepatitis is disclosed. The chemical makeup of the probe hCy-Tf-CA is shown in Equation 1. The fluorescence and photoacoustic signal of probe-only solution is very weak, the dual-modal signal was significantly increased after selectively reacting with O2·−. The probe has the advantages of early preparation, live-targeting ability, high selectivity and sensitivity and dual-modal imaging. The probe can in situ visualization of O2·− in early hepatic inflammation with fluorescent/photoacoustic dual-modal imaging, providing a potential strategy in biomedical field with broad application prospects.