PEG-Modified Zwitterionic Fluorescent Probe for Tumor Imaging
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Solution Overview
Problem
Current near-infrared fluorescent probes for tumor detection face challenges such as high tissue background signals, low tumor specificity, and complex synthesis processes, which hinder their effectiveness in precise tumor surgery navigation.
Innovation Solution
A polyethylene glycol modified zwitterionic fluorescent probe is developed, featuring a heptamethine chain with a phenoxy bridge and rigid ring structure, connected with sulfonic indole groups and polyethylene glycol chains. This probe includes a tumor-targeting ligand linked via a polyethylene glycol chain and an alkaline amino acid spacer, optimizing water solubility and reducing non-specific adsorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IRDye800CW fluorescent probe is used for tumor detection, then fluorescence intensity and stability are improved, but synthesis complexity and cost increase
Solution Approach 1:
The patent creates a simplified copy of IRDye800CW by replacing its complex asymmetric structure with a symmetric heptamethine cyanine structure (Formula I). This copy retains the essential fluorescence properties in the near-infrared region while dramatically simplifying the synthesis process. The symmetric structure allows for more straightforward chemical synthesis compared to the complex asymmetric structure of IRDye800CW, thus reducing both synthesis complexity and cost while maintaining fluorescence stability.
Solution Approach 2:
The patent modifies key structural parameters of the fluorescent probe by changing from the asymmetric IRDye800CW structure to a symmetric heptamethine cyanine structure with specific parameters: S1 and S2 are sulfonated indole groups, X is O, S, or Se, and n is 5-7 (preferably 6). These parameter changes maintain the near-infrared fluorescence properties while simplifying synthesis. The patent also optimizes the polymerization degree of polyethylene glycol chains (x and y are 1-10, preferably 3) to balance water solubility and synthesis ease.
2Quantity of substance
If multiple sulfonic acid groups are added to improve water solubility, then water solubility increases, but non-specific adsorption and background signal increase
Solution Approach 1:
The patent applies local quality modification by introducing polyethylene glycol chains at specific positions (connected to indole groups via sulfur atoms) rather than uniformly distributing charge-neutral groups throughout the molecule. This localized modification provides water solubility enhancement at the periphery of the molecule while keeping the core fluorescent structure intact. The polyethylene glycol chains (with polymerization degree x and y of 1-10, preferably 3) create hydrophilic regions that improve solubility without adding negative charges that would cause non-specific adsorption.
Solution Approach 2:
The patent creates a composite structure by combining the hydrophobic heptamethine cyanine core (which provides fluorescence) with hydrophilic polyethylene glycol chains (which provide solubility). This composite approach allows the molecule to achieve both water solubility and low non-specific adsorption. The polyethylene glycol chains act as hydrophilic shields that prevent the fluorophore from interacting non-specifically with biological tissues while maintaining excellent water solubility.
3Measurement precision
If tumor targeting ligand is added to improve tumor specificity, then tumor detection accuracy improves, but molecular complexity and synthesis difficulty increase
Solution Approach 1:
The patent segments the fluorescent probe into distinct functional modules: the heptamethine cyanine core (Formula I) provides fluorescence, the polyethylene glycol chains provide solubility and reduce non-specific adsorption, and the tumor targeting ligand (Ligand 1) provides specificity. This modular segmentation allows each component to be optimized independently and facilitates straightforward conjugation. The ligand is connected via a spacer group to the core structure, creating a clear separation between the fluorescent core and the targeting functionality, thus reducing overall molecular complexity while maintaining high tumor detection accuracy.
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 achieves a low tissue background signal, high tumor signal-to-noise ratio, and simplified synthesis, making it suitable for industrial production and clinical use in near-infrared fluorescence imaging, as well as potential applications in photoacoustic imaging, photothermal therapy, and other tumor treatments.
Implementation Method 1
near-infrared fluorescence imaging
Implementation Method 2
strong absorbance at the near-infrared region
Implementation Method 3
improve the water solubility of the dye
Implementation Method 4
non-specific adsorption of dye
Implementation Method 5
A tumor targeting ligand is connected with a luminescent group through one polyethylene glycol chain and one alkaline amino acid spacer
Data Source
AI summary
The present disclosure is a polyethylene glycol modified zwitterionic fluorescent probe. The core luminescent group of the fluorescent probe of the present disclosure is a heptamethine chain which is connected by a phenoxy bridge and has a rigid ring structure in the center. The two ends of the heptamethine chain are two sulfonic indole groups, and two polyethylene glycol chains are connected with the indole groups. A tumor targeting ligand is connected with a luminescent group through one polyethylene glycol chain and one alkaline amino acid spacer. The probe of the present disclosure can be connected with polypeptides, small molecules and antibodies having a tumor targeting function, thereby achieving near-infrared fluorescence imaging for tumor targeting. The probe of the present disclosure has good druggability, and is extremely suitable for industrial production and clinical promotion.