Fluorescent Chitosan Polymers for Stable Vascular Imaging
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Solution Overview
Problem
Existing fluorescent markers for visualizing glycosamine-containing structures, such as blood vessels, are chemically unstable, toxic, and inefficient, limiting their effectiveness in vascular imaging.
Innovation Solution
Development of fluorescent water-soluble polycationic chitosan polymers conjugated with polymethine dyes, which are chemically stable, non-toxic, and offer improved imaging efficiency by targeting glycosamine-containing structures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If MHI148 dye is used for vascular staining, then fluorescence imaging can be achieved, but chemical stability deteriorates due to sensitivity to chemical and photoinduced decomposition
Solution Approach 1:
The patent uses chitosan polymer as an intermediary carrier to conjugate with MHI148 dye. The chitosan backbone provides structural stability and protects the fluorescent dye from chemical and photoinduced decomposition, while still allowing the dye to maintain its fluorescence imaging capability. This mediator approach resolves the contradiction between achieving fluorescence and maintaining chemical stability.
Solution Approach 2:
The invention creates a composite material by conjugating MHI148 dye with chitosan polymer to form a stable fluorescent conjugate. The composite structure combines the fluorescent properties of MHI148 with the chemical stability and water solubility of chitosan, simultaneously achieving both fluorescence imaging capability and enhanced chemical stability.
2Illumination intensity
If PEI is used as a carrier for fluorescent dye, then vascular visualisation can be achieved, but toxicity worsens due to cellular toxicity
Solution Approach 1:
The patent changes the chemical parameter of the polymer carrier from polyethyleneimine (PEI) to chitosan. This parameter change maintains the polycationic nature and glycosamine-containing structure necessary for vascular binding, while fundamentally altering the toxicity profile from highly toxic PEI to biocompatible chitosan, thus resolving the toxicity issue while preserving imaging functionality.
Solution Approach 2:
The patent replaces the toxic but effective PEI carrier with chitosan, which is naturally biodegradable and biocompatible. This substitution uses a material that is inherently safer for biological applications, allowing the fluorescent marker to perform its visualisation function without causing cellular toxicity, effectively replacing a harmful substance with a benign alternative.
3Measurement precision
If blue and green region dyes are used for fluorescence imaging, then specific staining can be achieved, but tissue penetration depth worsens due to poor penetration and autofluorescence disturbance
Solution Approach 1:
The patent modifies the optical parameter of the fluorescent marker by selecting MHI148 dye, which emits in the red/near-infrared region rather than blue/green. This parameter change in emission wavelength simultaneously improves tissue penetration depth and reduces autofluorescence interference, while the glycosamine-containing chitosan structure maintains specific binding to vascular structures.
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 fluorescent markers provide reproducible, efficient, and non-toxic imaging of glycosamine-containing structures, offering enhanced spatial resolution and reduced toxicity compared to previous markers.
Implementation Method 1
Fluorescent water-soluble polycationic chitosan polymers and use thereof as imaging agents for imaging glycosamine-containing structures
Implementation Method 2
MHI148-PEI uses branched PEI of molecular weight 70 kDa, conjugated to a cationic cyanine 7 dye and binds to glycosamine containing biological structures basing on an electrostatic interaction
Data Source
Figure 1(a)~1(f)
Figure 2(a)~2(b)
Figure 2(c)
AI summary
A fluorescent water-soluble polycationic chitosan polymer having a general formula (I) and salts thereof: wherein a is an integer between 220 and 11,200; R1 and R2 are independently selected from the group consisting of CH3CO and H, provided that at least 25% of the O-positions of the chitosan polymer structure is substituted with CH3CO; R7 is selected from the group consisting of CH3CO, H and Dye, provided that (i) at least one Dye residue is present in the chitosan polymer structure, (ii) and at least 15% of the N-positions of the chitosan polymer structure is substituted with CH3CO; Dye is a polymethine dye, having a general formula (II) : wherein W represents 4-8 carbon atoms forming a benzo-condensed or a naphto-condensed ring; R3 and R4 are independently selected from the group consisting of CH2CH3, (CH2)3SO3-, (CH2)3N+(CH3)3; R5 and R6 are independently selected from the group consisting of H, SO3-; Q is selected from the group consisting of wherein D is selected from the group consisting of