Chlorin Derivative Sonodynamic Therapy System
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Solution Overview
Problem
Current photodynamic and sonodynamic therapies face challenges such as limited selectivity, short radiation wavelengths, poor water solubility, and inability to comprehensively treat deep-seated tumors, particularly in cases of systemic metastasis, due to limitations in existing photosensitizers and ultrasound treatment systems.
Innovation Solution
Development of a chlorin derivative with improved water solubility and longer absorption wavelength, combined with an ultrasound medical system for comprehensive sonodynamic therapy, allowing flexible treatment parameters and enhanced tissue penetration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If photodynamic therapy is used to treat tumors, then tumor cells can be killed through generation of singlet oxygen and free radicals, but the treatment is inadequate for tumors deep in the body due to limited tissue penetration of light
Solution Approach 1:
The patent combines photodynamic therapy and sonodynamic therapy into a dual-modality treatment system. The photosensitizer compound can be activated by either light (for superficial tumors) or ultrasound (for deep tumors), merging the advantages of both therapies into a single therapeutic agent that addresses both treatment depth and efficacy.
Solution Approach 2:
The photosensitizer compound is designed to function in multiple modes: it can act as a photosensitizer for PDT when activated by light, and as a sonosensitizer for SDT when activated by ultrasound. This multi-functionality allows a single compound to treat both superficial and deep-seated tumors, overcoming the depth limitation of traditional PDT.
2Ease of operation
If sonodynamic therapy is used to treat deep tumors, then treatment can be performed without endoscope and causes no pain, but the existing ultrasound treatment systems are single-head transducers requiring tens of hours of continuous work for systemic treatment
Solution Approach 1:
The ultrasound treatment system is segmented into multiple independent transducer heads that can operate simultaneously. Each transducer head can treat different body regions independently, allowing parallel processing of multiple tumor sites. This segmentation reduces the total treatment time from tens of hours to a manageable duration while maintaining comprehensive coverage.
Solution Approach 2:
The system transitions from a single-head (one-dimensional) ultrasound transducer to a multi-head (multi-dimensional) configuration. By adding spatial dimensions with multiple transducer heads positioned at different locations, the system achieves simultaneous treatment of multiple body regions, dramatically reducing treatment time while maintaining ease of operation.
3Reliability
If existing photosensitizers are used, then photodynamic therapy can be performed, but they have large differences in selectivity to tumor cells, short radiation wavelength, narrow therapeutic window, and poor solubility under physiological conditions
Solution Approach 1:
The patent employs a composite molecular structure combining porphyrin and phthalocyanine units linked by methine bridges. This composite structure integrates the advantages of both components: porphyrin provides high tumor selectivity and photostability, while phthalocyanine extends the absorption wavelength to the near-infrared region. The resulting compound achieves both high selectivity and an expanded therapeutic window.
Solution Approach 2:
The molecular structure is optimized by adjusting parameters such as the number of methine bridges (n=2-7), substituent types (R1-R8 groups), and metal coordination (M). These parameter changes systematically improve the compound's properties: extending absorption wavelength to 650-850 nm, enhancing water solubility through hydrophilic substituents, and improving tumor selectivity through optimized molecular recognition.
4Length of stationary object
If photosensitizers with longer absorption wavelength are developed, then tissue penetration is improved, but water solubility and other physiological properties may be compromised
Solution Approach 1:
The patent systematically varies molecular parameters to achieve the desired balance. By introducing hydrophilic substituents (such as carboxyl, hydroxyl, or sulfonate groups as R1-R8), the compound's water solubility is enhanced without significantly altering the core porphyrin-phthalocyanine chromophore that provides the extended absorption wavelength. This parameter optimization allows simultaneous achievement of long wavelength absorption (650-850 nm) and high water solubility.
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 chlorin derivative effectively generates reactive oxygen species, reduces tumor volume, inhibits metastasis, and shortens treatment time, providing a more selective and effective treatment for both superficial and deep tumors with minimal side effects.
Implementation Method 1
Sonodynamic therapy (SDT) is a new therapy developed on the basis of photodynamic therapy (PDT) for the clinical treatment of malignant and tumors deep in the body. Using ultrasound as the driving force, at the tumor site where the sonosensitizer is enriched, ultrasonic cavitation is formed, and singlet oxygen capable of killing tumor cells and related biochemical reactions are generated
Implementation Method 2
Using ultrasound as the driving force, at the tumor site where the sonosensitizer is enriched, ultrasonic cavitation is formed, and singlet oxygen capable of killing tumor cells and related biochemical reactions are generated
Implementation Method 3
Photodyamic therapy (PDT) is a novel method for treating tumors or other diseases by using photosensitive drugs and laser irradiation. Particularly, photodynamic therapy is carried out by using a photosensitizer to generate singlet oxygen (1O2) and free radicals under radiation at a specific wavelength
Data Source
AI summary
The present disclosure relates to a chlorin derivative or a pharmaceutically acceptable salt thereof, a preparation method thereof, an anti-tumor composition including the chlorin derivative or the pharmaceutically acceptable salt thereof, use of the chlorin derivative or the pharmaceutically acceptable salt thereof in the treatment of a tumor, and a combination of the chlorin derivative or the pharmaceutically acceptable salt thereof and an ultrasound medical system. The chlorin derivative or the pharmaceutically acceptable salt thereof has a structure represented by formula (I), and the ultrasonic medical system comprises a transducer ultrasonic bed and a contact agent. The chlorin derivative of the present disclosure can be used in photodynamic therapy and sonodynamic therapy, thereby effectively inhibiting and treating cancer.