H2O2-Responsive NIR Probe Crosslinking for Tumor Retention
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing NIR fluorescent dyes used for tumor imaging have short residence times in the body due to rapid excretion by biological tissues, impairing imaging effectiveness.
Innovation Solution
A H2O2-responsive crosslinking NIR molecular probe is developed, which cross-links at the tumor site using 3,5-dioxocyclohexanecarboxylic acid to react with tumor microenvironment proteins, enhancing long-term retention and imaging efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If traditional NIR fluorescent dyes are used for tumor imaging, then imaging can be performed, but the residence time in the body is too short due to rapid excretion by biological tissues
Solution Approach 1:
The probe is pre-modified with H2O2-responsive crosslinking groups (3,5-dioxocyclohexanecarboxylic acid) before administration. Upon reaching the tumor microenvironment, these groups automatically activate and form crosslinked networks with proteins, creating a retained complex that prevents excretion. This preliminary structural preparation enables the probe to transition from a freely excretable state to a retained complex state in response to tumor-specific conditions.
Solution Approach 2:
Proteins in the tumor microenvironment serve as intermediaries between the NIR probe and the crosslinking mechanism. The H2O2-responsive groups on the probe mediate the formation of crosslinked complexes with these proteins, creating a stable association that prevents renal clearance while maintaining the probe's imaging function. This intermediary mechanism allows selective retention at the tumor site without affecting systemic circulation.
2Reliability
If the probe is designed to stay at the tumor site longer, then imaging effect improves, but the probe may be excreted too quickly before achieving sufficient retention
Solution Approach 1:
The probe exhibits different properties in different locations: in normal circulation, it remains as a freely soluble molecule that can be cleared; upon encountering the tumor microenvironment with H2O2, it undergoes crosslinking to form a retained complex. This local quality change—controlled by the tumor-specific H2O2 environment—enables selective retention at the tumor site while maintaining rapid clearance from normal tissues, thereby improving imaging reliability without compromising residence time.
3Duration of action of moving object
If crosslinking groups are added to the NIR dye to enable H2O2-responsive crosslinking, then long-term retention is achieved, but the molecular structure becomes more complex
Solution Approach 1:
The probe combines the NIR fluorescent dye (Cy5 or similar) with H2O2-responsive crosslinking groups (3,5-dioxocyclohexanecarboxylic acid) to create a composite molecular structure. This composite design integrates the imaging function of the dye with the retention function of the crosslinking groups, enabling dual functionality in a single molecule. The crosslinking groups are strategically positioned to respond to H2O2 and form networks with proteins, achieving long-term retention without significantly complicating the overall molecular architecture.
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 prolonged retention and improved fluorescence imaging in tumors by covalently bonding to proteins, overcoming the limitations of short residence times and shallow penetration depth.
Implementation Method 1
H2O2 responds to the cross-linked NIR molecular probe to generate a photocross-linking reaction under the trigger of the tumor microenvironment
Implementation Method 2
NIR fluorescent dye detection technology can achieve in-situ, targeted non-invasive dynamic monitoring of cancer
Data Source
AI summary
The present invention discloses H2O2 responsive crosslinking NIR molecular probe for tumor microenvironment and application therefor. The preparation method includes the following steps: the amide condensation of 2-propynylamine and Fmoc-Lys(Boc)-OH to obtain compound A01-01; removing protecting groups from compound A01-01, to obtain compound C1-2; reacting compound C1-2 and NHS-activated (3-carboxypropyl)triphenylphosphonium bromide, to obtain compound C1-3; removing protecting groups from compound C1-3, to obtain compound C1-4; reacting compound C1-4 with NHS-activated 3,5-dioxocyclohexane carboxylic acid, to obtain a compound C1-5; and reacting compound C1-5 with NIR dye, to obtain a H2O2 responsive crosslinking NIR molecular probe for tumor microenvironment. The probe itself uses H2O2 in a tumor microenvironment for crosslinking on a tumor site, achieving the goal of a long-term retention, thereby improving a result of tumor imaging, and providing a novel strategy and means for improving long-term retention of a NIR molecular probe at a tumor site.