Anionic Bacteriochlorophyll Derivatives for Deep-Tissue Photodynamic Therapy
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Solution Overview
Problem
Current photodynamic therapy (PDT) agents, such as porphyrins, suffer from limitations including weak absorption in the visible spectral range, prolonged skin phototoxicity, and poor differentiation between tumor and non-tumor tissues, necessitating the development of more effective sensitizers with improved spectral characteristics and stability.
Innovation Solution
Development of water-soluble anionic bacteriochlorophyll derivatives with negatively charged groups, such as sulfonate or phosphonate, which enhance vascular targeting and reduce skin phototoxicity by remaining in circulation and accumulating selectively in tumor vasculature, thereby improving PDT efficacy and reducing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Use of energy by moving object
If porphyrins are used as photosensitizing agents in PDT, then the treatment can be performed with available drugs, but the absorption in the visible spectral range is weak which limits treatment to shallow tumors
Solution Approach 1:
The patent modifies the molecular structure of bacteriochlorophyll by changing parameters such as adding negatively charged groups (sulfonate, phosphonate) and modifying side chains to extend absorption into the near-infrared region (650-850 nm), enabling deeper tissue penetration while maintaining photosensitizing efficacy
Solution Approach 2:
The invention creates composite molecular structures by combining the bacteriochlorophyll core with various substituent groups and charged moieties, resulting in a composite photosensitizer that achieves both deep tissue penetration and selective tumor targeting
2Duration of action of moving object
If current photosensitizers are used, then the treatment can proceed, but accumulation and long retention in patient skin leads to prolonged skin phototoxicity
Solution Approach 1:
The patent introduces negatively charged groups and hydrophilic moieties that create local polarity differences, causing the photosensitizer to preferentially accumulate in tumor tissues with different membrane properties while reducing retention in normal skin tissues, thereby minimizing phototoxicity
Solution Approach 2:
By modifying molecular parameters such as adding charged groups and changing solubility characteristics, the patent achieves rapid clearance from normal tissues while maintaining selective accumulation in tumors, reducing the duration of phototoxic effects
3Reliability
If porphyrins are used as photosensitizers, then the treatment can be performed, but there is small or no differentiation between PDT effect on illuminated tumor and non-tumor tissues
Solution Approach 1:
The patent employs local quality differentiation by incorporating charged groups and hydrophilic moieties that exploit differences in tumor versus normal tissue properties, enabling selective accumulation in tumor vasculature and preferential PDT effect on tumor tissues
Solution Approach 2:
The modified bacteriochlorophyll derivatives act as intermediaries that selectively interact with tumor tissue through electrostatic and hydrophilic interactions, mediating selective drug accumulation and targeted photodynamic effect while sparing normal tissues
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 water-soluble bacteriochlorophyll derivatives exhibit enhanced phototoxicity and selectivity for tumor tissues, with rapid clearance from the body and minimal retention in normal tissues, allowing for effective treatment of tumors and vascular diseases while minimizing skin damage.
Implementation Method 1
Photodynamic therapy (PDT) is a non-surgical treatment of tumors in which non-toxic drugs and non-hazardous photosensitizing irradiation are combined to generate cytotoxic reactive oxygen species in situ
Implementation Method 2
water-soluble anionic bacteriochlorophyll derivatives with negatively charged groups, such as sulfonate or phosphonate, which enhance vascular targeting and reduce skin phototoxicity by remaining in circulation and accumulating selectively in tumor vasculature
Data Source
AI summary
The invention provides anionic water-soluble tetracyclic and pentacyclic bacteriochlorophyll derivatives (Bchls) containing at least one, preferably two or three, negatively charged groups and/or acidic groups that are converted to negatively charged groups at the physiological pH, preferably Bchls having a group COO<−>, COS<−>, SO3<−>, PO3<2−>, COOH, COSH, SO3H, and/or PO3H2 bound through an ester or amide bond to one or more of the positions 17<3>, 13<3>, and 3<2> of the tetracyclic or pentacyclic Bchl molecule, for photodynamic therapy and diagnosis.