Small Molecule NIR-II Fluorophores for Deep Tissue Imaging
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Solution Overview
Problem
Current near-infrared (NIR) fluorophores for imaging in the NIR-II window face challenges such as slow excretion, toxicity concerns, and the need for encapsulation in polymer matrices due to hydrophobicity, limiting their clinical translation and imaging depth and resolution.
Innovation Solution
Development of novel small molecule NIR-II fluorophores modified with hydrophilic polymers or sulfonic acids like taurine, enabling rapid excretion and high biocompatibility, along with targeting ligands for enhanced imaging and photothermal therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If inorganic nanomaterials are used as NIR-II fluorophores, then imaging quality and depth are improved, but excretion is slow and toxicity concerns increase
Solution Approach 1:
The patent changes the material composition from inorganic nanomaterials to organic small molecules, fundamentally altering the chemical parameters to achieve both high imaging quality and rapid renal excretion. The small molecule structure allows filtration by kidney glomeruli while maintaining NIR-II fluorescence properties.
Solution Approach 2:
The patent employs small molecule fluorophores that are rapidly excreted and replaced, rather than persisting in the body like nanomaterials. This disposable approach reduces long-term toxicity accumulation while maintaining imaging effectiveness through repeated dosing if needed.
2Measurement precision
If molecular NIR-II fluorophores are used, then imaging resolution is improved, but they must be encapsulated in polymer matrices due to hydrophobicity, increasing size and reducing excretion
Solution Approach 1:
The patent modifies molecular parameters by introducing hydrophilic groups (sulfonates, carboxylates, hydroxyls) directly into the small molecule structure, changing the solubility parameter from hydrophobic to hydrophilic. This eliminates the need for polymer encapsulation while maintaining molecular imaging resolution.
Solution Approach 2:
The patent extracts the fluorophore from the polymer matrix environment, allowing the small molecule to function independently in aqueous biological systems. The hydrophilic modification enables the molecule to operate without the protective polymer shell, simplifying the overall system.
3Length of stationary object
If imaging depth is increased in NIR-II window, then tissue penetration is improved, but background autofluorescence and scattering must be minimized
Solution Approach 1:
The patent utilizes the color (wavelength) change from NIR-I to NIR-II region, where tissue autofluorescence naturally decreases. The small molecule fluorophores are designed to emit in the 1000-1700 nm range where biological tissues have minimal endogenous fluorescence, improving signal-to-background ratio at greater depths.
4Reliability
If small molecule fluorophores are used for rapid excretion, then renal filtration is improved, but molecular weight must remain below renal threshold
Solution Approach 1:
The patent carefully controls the molecular weight parameter by designing compact small molecule structures with multiple hydrophilic groups that enhance water solubility and renal filtration. The molecules are kept below the 40 kDa glomerular filtration threshold while incorporating sufficient hydrophilic character for rapid excretion.
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 new fluorophores provide high-resolution imaging deep within tissues, rapid renal excretion, and minimal toxicity, enabling improved tumor detection and image-guided surgery with enhanced tumor-to-normal tissue ratios and photothermal effects.
Implementation Method 1
fluorescent imaging and photothermal therapy in the second near-infrared window
Implementation Method 2
photothermal therapy in the second near-infrared window
Data Source
AI summary
Disclosed is a small molecule dye for use in imaging in the near-infrared window, namely between 1000 nm-1700 nm wavelength. The present dyes are also useful for photoacoustic imaging and photothermal therapy. The dyes have a structure of a D-A-D (donor-acceptor-donor) fluorescent compound core and side chains rendering the compounds water soluble and easily conjugated to hydrophilic polymers and/or targeting ligands. Further disclosed is compound, CH1055 that can be PEGylated, conjugated to a targeting ligand, or conjugated to taurine. Key steps utilized to assemble the core structure of the target included a cross-Suzuki coupling reaction, iron reduction and N-thionylaniline induced ring closure. Four carboxylic acid groups were introduced into the donor-acceptor-donor (D-A-D) type fluorescent compound to impart a certain aqueous solubility and to allow facile conjugation to targeting ligands.