Polysarcosine Polymer Conjugate for Photoacoustic Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Near-infrared dye-conjugated PEG exhibits high tumor accumulation but has low tumor/blood ratio due to high retentivity in blood, limiting its effectiveness in photoacoustic imaging.
Innovation Solution
A polymer with a polysarcosine main chain conjugated with a near-infrared dye, such as indocyanine green, is developed, which utilizes enzymatic degradation to increase tumor accumulation and reduce blood concentration, enhancing the tumor/blood ratio.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If near-infrared dye is conjugated with PEG, then half-life in blood is prolonged and tumor accumulation is enhanced, but retentivity in blood becomes too high resulting in low tumor/blood ratio
Solution Approach 1:
The invention changes the chemical composition parameter of the polymer from PEG to polysarcosine, which fundamentally alters the biological interaction properties. Polysarcosine exhibits different metabolic pathways and clearance mechanisms compared to PEG, enabling prolonged circulation without excessive blood retention, thus resolving the contradiction between extended half-life and adequate tumor/blood ratio
Solution Approach 2:
The invention creates a composite structure by conjugating near-infrared dye with polysarcosine polymer. This composite material combines the tumor-targeting capability of the dye with the favorable pharmacokinetic properties of polysarcosine, achieving both prolonged circulation and high tumor accumulation while maintaining low blood background
2Quantity of substance
If PEG is used as polymer backbone, then tumor accumulation is high, but blood retentivity is also high reducing imaging contrast
Solution Approach 1:
The invention changes the polymer backbone composition from PEG to polysarcosine, which has different biodegradation and clearance properties. Polysarcosine can be metabolized by proteases in the tumor microenvironment, allowing selective accumulation in tumors while being cleared from blood circulation, thereby reducing blood retentivity and improving imaging contrast
3Duration of action of moving object
If contrast agent remains in blood for long time, then half-life is prolonged, but tumor imaging contrast decreases due to high background signal
Solution Approach 1:
The invention introduces dynamic behavior to the contrast agent through the use of polysarcosine, which can change its distribution and clearance rate based on the local environment. The polymer exhibits enhanced stability in blood circulation but undergoes selective degradation or accumulation in the tumor microenvironment, creating dynamic contrast enhancement over time while maintaining adequate circulation duration
Solution Approach 2:
The invention changes the temporal distribution parameter of the contrast agent by using polysarcosine conjugation. This results in a biphasic distribution pattern with initial circulation phase followed by selective tumor accumulation phase, allowing optimization of both circulation time and imaging contrast by timing the imaging procedure appropriately
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 polymer achieves a high tumor/blood ratio, allowing for effective photoacoustic imaging by accumulating more in tumors and being rapidly cleared from the blood, thereby enhancing contrast and imaging quality.
Implementation Method 1
D represents a dye backbone of a dye having absorption in the near-infrared region
Implementation Method 2
measuring the intensity and the time of generation of a photoacoustic signal emitted from a substance (optical absorber) that absorbs light
Implementation Method 3
utilizes enzymatic degradation to increase tumor accumulation and reduce blood concentration
Data Source
AI summary
An object is to provide a polymer having a high tumor/blood ratio. The present invention provides a polymer represented by the following formula (P1):wherein in the formula (P1), R represents any of a residue derived from a polymerization initiator, or a functional group; A may not be present, and when present, A represents any of a low-molecular compound, a dye, a reporter molecule, a target-binding molecule, a polymer or D; L represents a linker and L may not be present; n1 represents an integer of 1 or more; and D represents a dye backbone of a dye having absorption in the near-infrared region.