NIR Fluorescence Tumor-Targeting Probe for Surgical Margins
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Solution Overview
Problem
Current breast cancer surgery methods struggle with achieving negative margins due to challenges in distinguishing between healthy and malignant tissues, leading to high re-resection rates and residual lesions, despite the use of traditional imaging modalities like CT, MRI, and fluorescence imaging techniques like ICG face limitations in specificity and stability.
Innovation Solution
Development of a near-infrared (NIR) fluorescence imaging probe, ICG-p28, composed of the clinically nontoxic tumor-targeting peptide p28 and the FDA-approved dye indocyanine green (ICG), which enhances intraoperative imaging to accurately identify tumor margins and reduce re-excision rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional imaging modalities (CT, MRI, PET) are used to assess tumor lesions, then tumor detection capability is improved, but intraoperative imaging accuracy deteriorates due to inability to provide real-time guidance during surgery
Solution Approach 1:
The patent applies preliminary action by administering the NIR fluorescent probe to the patient before surgery and allowing it to accumulate in tumor tissue overnight. This pre-positioning of the imaging agent enables real-time intraoperative visualization without requiring complex imaging equipment during the actual surgical procedure, thus resolving the contradiction between preoperative detection accuracy and intraoperative guidance timeliness
2Ease of operation
If ICG dye is used for fluorescence imaging, then real-time visualization capability is improved, but tumor-specific targeting deteriorates due to passive dye distribution and short half-life
Solution Approach 1:
The patent creates a composite fluorescent probe by conjugating ICG dye with a tumor-targeting peptide (such as RGD or TAT peptide). This composite structure combines the real-time visualization capability of ICG with the tumor-specific targeting ability of the peptide, allowing the probe to actively home in on tumor cells while maintaining fluorescent properties. The peptide component enables specific binding to tumor cell surfaces, thereby resolving the contradiction between ease of real-time visualization and measurement precision of tumor-specific identification
Solution Approach 2:
The patent modifies the physical and chemical parameters of ICG by conjugating it with targeting peptides, which changes its biodistribution characteristics from passive circulation to active tumor accumulation. This parameter change extends the effective imaging window and enhances tumor contrast, thereby improving both real-time visualization and tumor-specific identification simultaneously
3Manufacturing precision
If wider negative margins are excised to ensure complete tumor removal, then residual tumor DNA is reduced, but loss of healthy tissue increases and cosmetic outcomes deteriorate
Solution Approach 1:
The patent replaces the mechanical judgment system (surgeon's visual and tactile cues) with an optical detection system (NIR fluorescence imaging). By using the fluorescent probe to highlight tumor margins in real-time, surgeons can precisely identify the extent of tumor infiltration without relying on arbitrary margin widths. This substitution allows for minimal yet adequate resection, removing only the necessary tissue while preserving healthy structures, thus resolving the contradiction between achieving tumor-free margins and minimizing healthy tissue loss
Solution Approach 2:
The patent implements real-time feedback during surgery by using NIR fluorescence imaging to continuously monitor the resection margins. As the surgeon removes tissue, the fluorescence signal provides immediate feedback on whether tumor cells remain at the margin, allowing dynamic adjustment of the resection boundary. This feedback mechanism enables precise control of margin width, ensuring complete tumor removal while minimizing healthy tissue excision, thereby resolving the contradiction between manufacturing precision of tumor-free margins and loss of substance in healthy 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
ICG-p28 significantly reduces residual tumor DNA at the margin site by 6.6×103-fold, improving tumor recurrence rates to 92% specificity, enabling precise tumor cell identification and complete resection in breast cancer models.
Implementation Method 1
its ability to readily nonspecifically bind to plasma proteins, and its lack of a tumor-specific ligand-receptor interaction mechanism as a passive fluorescent dye
Implementation Method 2
Near-infrared (NIR) imaging is an emerging biomedical imaging modality for fluorescence-guided surgery because of its significant light absorption, ability to assist in real-time visualization
Implementation Method 3
In vivo imaging in the NIR range (700-900 nm) is superior to that in the visible spectrum owing to its low scattering, negligible tissue autofluorescence, and relatively high tissue penetration
Data Source
AI summary
A unique near-infrared (NIR) fluorescence imaging probe, ICG-p28, composed of the clinically nontoxic tumor-targeting peptide p28 and the FDA-approved NIR dye indocyanine green (ICG) have been analyzed for in vivo kinetics and optimized for clinical practice. Intraoperative imaging with ICG-p28 was used to identify small (≤1 mm) lymph nodes (LNs) containing cancer cells. Image-guided surgery with ICG-p28 showed an over 6.6×103-fold reduction in residual normalized tumor DNA at the margin site relative to control approaches, resulting in an improved tumor recurrence rate (92% specificity) in multiple animal models.