CA IX-Targeted NIR Dyes for Deep Tissue Imaging
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Solution Overview
Problem
Current methods for diagnosing and treating cancer, particularly hypoxic tumors, face challenges due to the resistance of hypoxic tumor cells to radiation and chemotherapeutics, and the difficulty in detecting tumors buried deep within tissues, leading to poor prognosis and recurrence rates.
Innovation Solution
Development of CA IX-targeted near-infrared (NIR) dyes that specifically bind to carbonic anhydrase IX (CA IX), allowing for deep tissue penetration and high tumor-to-background ratios, enabling precise imaging and surgical guidance by illuminating CA IX-expressing cells with near-infrared light.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional dyes are used for tumor imaging, then the imaging can be performed, but the tumor-to-background ratio is low and deep tissue penetration is insufficient
Solution Approach 1:
The patent changes the wavelength parameter of the dye to near-infrared range (700-900 nm), which enables deep tissue penetration and reduces background interference from autofluorescence, thereby improving tumor detection precision and tumor-to-background ratio simultaneously
Solution Approach 2:
The patent introduces a targeting ligand as an intermediary that specifically binds to CA IX on tumor cells, mediating the attachment of the NIR dye to the target tissue. This ensures specific accumulation at the tumor site while reducing non-specific background signal
2Reliability
If hypoxic tumor cells are targeted, then the specific pathology can be addressed, but the resistance to radiation and chemotherapeutics remains
Solution Approach 1:
The patent exploits the hypoxic tumor cells' own overexpression of CA IX as a self-identifying feature. The NIR dye-conjugate targets this endogenous marker, allowing the hypoxic cells to effectively mark themselves for detection without requiring external intervention, thereby achieving high diagnostic accuracy while bypassing their therapeutic resistance mechanisms
3Measurement precision
If early diagnosis is achieved, then the prognosis can be improved, but the tumors are often buried deep within tissues making detection difficult
Solution Approach 1:
The patent changes the optical wavelength to near-infrared range which has longer penetration depth in biological tissues compared to visible light. This enables early tumor detection even when tumors are buried deep within tissues, as the NIR light can reach and detect the tumor signal through several centimeters of tissue
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 CA IX-targeted NIR dyes provide enhanced specificity and sensitivity for detecting CA IX-expressing cells, facilitating early diagnosis and improved surgical outcomes by clearly visualizing tumor boundaries, even in deeply seated cancers, thereby improving patient prognosis.
Implementation Method 1
CA IX-targeted near-infrared (NIR) dyes that specifically bind to carbonic anhydrase IX (CA IX)
Implementation Method 2
allowing for deep tissue penetration and high tumor-to-background ratios, enabling precise imaging and surgical guidance by illuminating CA IX-expressing cells with near-infrared light
Data Source
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AI summary
The present disclosure relates to compounds that are useful as near-infrared fluorescence probes, wherein the compounds include i) a ligand that binds to the active site of carbonic anhydrase, ii) a dye molecule, and iii) a linker molecule that comprises an amino acid, amide, ureido, or polyethylene glycol derivative thereof. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.