NIR Fluorophore Probe for Senescent Cell Detection

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Solution Overview

Problem

Current methods for visualizing senescent cells in vivo lack effective probes that can specifically detect senescence-associated β-galactosidase (SA-β-Gal) activity, limiting real-time monitoring and treatment evaluation of senescence-related diseases.

Innovation Solution

A novel probe comprising a biomarker-triggered moiety, a near-infrared (NIR) fluorophore reporter, a self-immolative linker, and a self-immobilizing moiety that 'turns on' fluorescence in the presence of SA-β-Gal, enabling specific visualization of senescent cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fluorescent probes are used for β-gal detection, then detection capability is provided, but tissue autofluorescence interferes with signal detection in vivo

Engineering Contradiction:
Improvedetection capabilityVSAvoidtissue autofluorescence interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent transitions from conventional visible light fluorescent probes to near-infrared fluorescent probes, changing the emission wavelength parameter to 650-900 nm. This parameter change shifts the detection window away from the autofluorescence region, enabling specific detection of SA-β-Gal activity in vivo while minimizing tissue autofluorescence interference.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If existing β-gal detection methods are used, then detection is possible, but real-time monitoring in living subjects is not enabled

Engineering Contradiction:
Improvedetection capabilityVSAvoidreal-time monitoring capability
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The probe is designed with a self-activating mechanism where the fluorophore is masked by a galactoside moiety that is specifically recognized and hydrolyzed by SA-β-Gal. This self-service mechanism allows the probe to automatically activate and generate fluorescence signal only when encountering senescent cells, enabling real-time monitoring without external intervention.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If conventional probes are used, then detection is possible, but specific visualization of senescent cells in vivo is not achieved

Engineering Contradiction:
Improvedetection capabilityVSAvoidspecificity for senescent cells
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The probe incorporates a galactoside-triggered fluorophore system with localized specificity. The galactoside moiety is specifically recognized by SA-β-Gal, creating a local chemical interaction that activates fluorescence only at the site of senescent cells. This local quality approach ensures specific visualization of senescent cells while maintaining low background signal in non-senescent tissues.

Inventive Principle:
Principle #3Local quality

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 effectively differentiates senescent cells from normal cells, as demonstrated by increased fluorescence in cells treated with senescence-inducing agents, and shows promise for real-time imaging of senescence in tumors, providing a tool for evaluating treatment responses.

Implementation Method 1

a near infrared (NIR) fluorophore reporter

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

a self-immolative linker

Methodology Applied
Scientific EffectChemical decomposition: Decomposition (biological)

Data Source

PatentUS12005128B1Near infrared small molecule probes for the detection of cellular senescence
Publication Date: 2024.06.11 UNM RAINFOREST INNOVATIONS
  • US12005128B1 patent drawing
  • US12005128B1 patent drawing
  • US12005128B1 patent drawing

AI summary

A probe comprising a biomarker-triggered moiety, a near infrared (NIR) fluorophore reporter, a self-immolative linker and a self-immobilizing moiety for visualization of senescent cells and methods of use thereof.