Optical Sensor Conjugates for ROS/RNS Detection
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Solution Overview
Problem
Current probes for detecting reactive oxygen and nitrogen species (ROS/RNS) in vivo are hindered by unfavorable washout kinetics, poor dye properties, and activation by numerous ROS, making them impractical for imaging inflammation-related diseases.
Innovation Solution
Development of optical sensor conjugates comprising a fluorogenic small molecule linked to a particle, which oxidizes and releases a fluorescent molecule upon reacting with ROS/RNS, allowing for detection through fluorescence imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If small molecule probes are used for detecting ROS/RNS, then detection capability is achieved, but washout kinetics are unfavorable and duration of action is too short
Solution Approach 1:
The patent combines a fluorogenic small molecule with a nanoparticle carrier to form a sensor conjugate. The nanoparticle provides prolonged circulation time and sustained delivery to the target site, while the fluorogenic molecule maintains its detection capability. This merging resolves the contradiction by extending the duration of action without sacrificing detection precision.
Solution Approach 2:
The sensor conjugate is a composite material consisting of a fluorogenic small molecule attached to a nanoparticle. The nanoparticle component provides favorable pharmacokinetics and extended circulation, while the fluorogenic molecule provides detection function. This composite structure simultaneously achieves both detection capability and prolonged duration of action.
2Measurement precision
If conventional probes are used, then detection is possible, but specificity for relevant ROS is poor and activation by numerous ROS occurs
Solution Approach 1:
The fluorogenic small molecule is designed with specific chemical functionality that provides selective reactivity toward particular ROS species (such as HOCl or ONOO−). This local chemical property ensures that only the target ROS activates the fluorogenic signal, while other ROS do not interfere, thereby achieving high specificity without compromising detection capability.
3Measurement precision
If small molecule probes are used, then detection is achieved, but dye properties are poor
Solution Approach 1:
The patent merges a fluorogenic small molecule with a nanoparticle carrier. The nanoparticle can incorporate high-quality fluorescent dyes with superior optical properties, while the fluorogenic molecule provides ROS-specific activation. This combination resolves the contradiction by achieving both good dye properties and specific detection capability.
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 optical sensor conjugates provide improved pharmacokinetics and specificity for ROS/RNS, enabling effective imaging of inflammation-related diseases by releasing a fluorescent molecule upon reaction, thereby enhancing detection sensitivity and duration.
Implementation Method 1
The fluorogenic small molecule can be oxidized in vivo by ROS/RNS causing the small molecule to be released from the linker and fluoresce
Implementation Method 2
The fluorescent small molecule can be detected, e.g., by microscopy
Data Source
AI summary
The present invention provides methods and compositions based on optical sensor conjugates that are useful for detecting reactive oxygen, reactive nitrogen, or both species that are a direct result of inflammation caused by tissue damage.