Tumor-Targeting Fluorescent Probe Composition for Selective Imaging
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Solution Overview
Problem
Conventional fluorescent dyes lack targeting specificity, leading to accumulation in both tumor and normal tissues, causing over-resection and damage to surrounding healthy structures during fluorescence-guided surgery, while existing folate receptor-targeted probes suffer from reduced receptor affinity and undesired accumulation in normal tissues.
Innovation Solution
Development of fluorescent probe compounds with a pyrrolo[2,3-d]pyrimidine core structure as a targeting ligand, conjugated to a fluorescent dye via a linker molecule, enhancing tumor-specific affinity and retention, and utilizing specific amino groups or amide derivatives for improved targeting and fluorescence properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorescent dyes are used for tumor imaging, then the imaging coverage is broad, but the targeting specificity is poor leading to accumulation in normal tissues
Solution Approach 1:
The patent applies local quality by designing fluorescent probes with specific molecular structures (pyrrolo[2,3-d]pyrimidine core) that confer different binding affinities to different tissue types. The probe selectively accumulates in tissues with high folate receptor expression while avoiding normal tissues, achieving localized accumulation based on molecular characteristics rather than uniform distribution.
Solution Approach 2:
The patent utilizes parameter changes by modifying the chemical structure of the fluorescent probe, specifically incorporating a pyrrolo[2,3-d]pyrimidine core with specific substituents. This structural modification changes the binding parameters to achieve high affinity for folate receptors while maintaining fluorescence properties, thereby improving targeting specificity without sacrificing imaging capability.
2Measurement precision
If folic acid conjugates are used as targeting ligands, then the tumor targeting is improved, but the receptor affinity is reduced
Solution Approach 1:
The patent applies parameter changes by replacing traditional folic acid conjugates with a pyrrolo[2,3-d]pyrimidine core structure that has optimized binding parameters. This structural modification enhances the binding affinity to folate receptors while maintaining effective tumor accumulation, resolving the contradiction between affinity and accumulation.
Solution Approach 2:
The patent uses composite materials by combining the pyrrolo[2,3-d]pyrimidine core structure with fluorescent dye moieties through specific linker molecules. This composite construction integrates the high-affinity binding capability of the pyrrolo core with the imaging capabilities of the fluorescent dye, achieving both high receptor affinity and effective tumor accumulation.
3Illumination intensity
If visible wavelength fluorescent dyes are used, then the fluorescence signal is strong, but the tissue penetration depth is limited
Solution Approach 1:
The patent applies parameter changes by selecting fluorescent dyes with optimized emission wavelengths that balance signal strength and tissue penetration. The probe design incorporates dyes that emit in the visible to near-infrared range, achieving sufficient fluorescence signal while improving penetration depth through appropriate wavelength selection.
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 compounds exhibit high specificity and sensitivity for tumor cells, enabling precise localization and visualization with minimal accumulation in normal tissues, suitable for clinical intraoperative navigation.
Implementation Method 1
This technique utilizes light of specific excitation wavelengths to induce fluorescence from either inherent tumor autofluorescence, retained fluorescent molecules, or exogenously administered fluorescent agents internalized by cells
Implementation Method 2
As folate receivers demonstrate high binding affinity for folic acid and folate conjugates (Kd≈10−9 M) and facilitate internalization via receiver-mediated endocytosis
Data Source
AI summary
The present invention relates to fluorescent probe compounds for tumor-targeted imaging, and methods of synthesis and use thereof. The compounds utilize, for the first time, an antitumor drug comprising a pyrrolo[2,3-d]pyrimidine core structure as a targeting ligand, which is conjugated to a fluorescent dye through a linker moiety. The structure of the compound is shown in Formula I. The compound demonstrates high affinity and selectivity for tumor cells expressing target receptors, enabling localization, qualitative and quantitative analysis through in vitro and in vivo tracking, receptor affinity studies, and mechanism of action investigations, thereby exhibiting high specificity, sensitivity, and visualization capability. The fluorescent probe of the present invention achieves rapid clearance from normal tissues while maintaining prolonged retention at tumor sites, thereby enabling in vivo diagnostic functionality. It demonstrates substantial clinical application potential for clinical intraoperative navigation.