Photosensitized Nitric Oxide Release via AlPcS4 and Alanosine
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Solution Overview
Problem
Current NO delivery systems, particularly those using photocontrollable NO donors with transition metals, face challenges such as systemic toxicity and the inability to generate peroxynitrite, a species that enhances toxic activity, due to the release of transition metal ions and instability of nitric oxide.
Innovation Solution
The photosensitized generation of NO from carbon-bound diazenium diolate compounds like alanosine using near-infrared radiation, which produces peroxynitrite in the presence of a sacrificial electron donor, such as hypoxanthine, to enhance therapeutic efficacy and reduce systemic toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If photocontrollable NO donors containing transition metals are used, then NO release can be controlled at the tissue site, but systemic toxicity occurs due to release of transition metal ions
Solution Approach 1:
The patent removes the transition metal component from the NO donor system. Instead of using metal-based NO donors, the invention employs organic diazeniumdiolate compounds that can be photoactivated without requiring metal centers, thereby eliminating the source of toxic metal ion release while preserving the ability to control NO release through light activation
Solution Approach 2:
The patent introduces an organic photosensitizing system as an intermediary mechanism to replace the direct metal-based photoactivation. The organic compounds absorb light energy and transfer it to the diazeniumdiolate group, enabling controlled NO release without direct involvement of toxic metal ions in the photochemical process
2Reliability
If conventional NO delivery systems are used, then NO can be transported to selected tissue, but the ability to generate peroxynitrite is lost due to instability of NO
Solution Approach 1:
The patent incorporates both the NO donor (diazeniumdiolate group) and the photosensitizing capability into a single molecular system that is stable during transport. The compound remains inert until light activation occurs at the target site, at which point it simultaneously generates NO and facilitates peroxynitrite formation through the photosensitized reaction with oxygen
Solution Approach 2:
The invention creates a composite functional system where the diazeniumdiolate compound integrates both NO donation and photosensitizing properties. This single molecular entity combines the functions of NO release and peroxynitrite generation, eliminating the need for separate unstable NO components while maintaining controlled delivery capability
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
This method effectively produces NO and peroxynitrite, offering a safer and more targeted delivery of nitric oxide, potentially useful in photodynamic therapies for malignancies, while minimizing systemic toxicity and enabling controlled release at specific tissue sites.
Implementation Method 1
the photosensitized generation of NO from carbon-bound diazenium diolate compounds like alanosine using near-infrared radiation
Implementation Method 2
Evidence supports the generation of peroxynitrite from air-saturated dye-alanosine solutions
Data Source
AI summary
The invention proposes the photosensitized generation of nitric oxide (NO) from alanosine (3-(hydroxynitrosoamino)-D,L-alanine) by aluminum phthalocyanine tetrasulfonate (AlPcS4). While NO is obtained in nitrogen-saturated solutions, the invention proposes that both NO and peroxynitrite are produced in air-saturated solutions. Enhancement of NO production occurs in the presence of ubiquinone-0. The invention evidence that NO is produced by the photosensitized oxidation of alanosine. Both NO and peroxynitrite are detected during photoirradiation of AlPcS4 in the presence of 2-methyl-2-nitrosopropane (MNP) and hypoxanthine, but not in the absence of hypoxanthine, in air-saturated solutions, where HX is acting as sacrificial electron donor, thus promoting superoxide formation.