S-Nitrosothiol-Modified Silica Particles for Tunable NO Release
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Solution Overview
Problem
Existing NO-releasing materials, such as S-nitrosothiol-modified silica particles, face limitations in NO storage capacity and controlled release kinetics due to restricted thiol functionalization on the surface and inability to tune particle size for therapeutic applications.
Innovation Solution
The method involves forming S-nitrosothiol-functionalized co-condensed silica particles by reacting a thiol-containing silane and a backbone alkoxysilane in a sol precursor solution, followed by nitrosation, to create particles with enhanced NO storage and controlled release profiles, with NO storage ranging from 0.01 to 10 µmol NO per mg and particle diameters between 200 nm to 700 nm.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If S-nitrosothiol-modified silica particles are prepared by surface grafting of SNAP, SNAC, or CysNO on fumed silica particles, then the particles can release NO, but the NO storage capacity is limited to 0.021-0.138 μmol mg⁻¹
Solution Approach 1:
The patent utilizes co-condensed silica particles with a porous structure that incorporates thiol groups within the particle matrix rather than just on the surface. This internal porosity and functional group distribution dramatically increases the NO storage capacity from 0.021-0.138 μmol mg⁻¹ to 0.01-10 μmol NO per mg particle, resolving the contradiction between limited surface grafting and low NO storage capacity.
Solution Approach 2:
The patent creates a composite material system by co-condensing silica precursors with thiol-containing silanes to form a unified particle structure where the thiol groups are integrated within the silica matrix. This composite approach enables both high NO storage capacity and controlled release kinetics, overcoming the limitations of simple surface grafting on fumed silica.
2Adaptability or versatility
If low molecular weight RSNOs (e.g., GSNO, SNAC, SNAP) are used as NO donors, then they can spontaneously release NO, but they lack tissue specific targeting and have uncontrollable NO release kinetics
Solution Approach 1:
The patent segments the NO donor function from the delivery vehicle by incorporating RSNO groups into larger silica particle scaffolds. This segmentation allows the particle size (200-700 nm) to be optimized for tissue targeting while the RSNO groups provide controlled NO release, resolving the contradiction between spontaneous release and controllable kinetics.
Solution Approach 2:
The patent introduces dynamic control over NO release by utilizing the size-tunable silica particles (200-700 nm) that can be engineered for specific tissue penetration and retention. The co-condensed structure allows dynamic adjustment of release kinetics while maintaining the ability to target specific tissues, overcoming the limitations of small molecule RSNOs.
3Length of moving object
If fumed silica particles (7-10 nm diameter) are used as the scaffold, then the particles can be functionalized with thiol groups, but the particle size is too small for therapeutic applications requiring larger sizes
Solution Approach 1:
The patent changes the particle size parameter from 7-10 nm fumed silica to 200-700 nm co-condensed silica particles through controlled co-condensation of silica and thiol-containing silane precursors. This parameter change increases both the therapeutic applicability and the total NO storage capacity per particle while maintaining the RSNO functional groups for controlled release.
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 approach results in S-nitrosothiol-functionalized co-condensed silica particles with increased NO storage capacity and controlled release, providing enhanced stability and tunable particle size for therapeutic applications, overcoming previous limitations of surface-restricted functionalization and size variability.
Implementation Method 1
reacting a thiol-containing silane and a backbone alkoxysilane in a sol precursor solution that comprises water to form thiol-functionalized co-condensed silica particles
Implementation Method 2
reacting a thiol-containing silane and a backbone alkoxysilane in a sol precursor solution that comprises water
Implementation Method 3
reacting the thiol-functionalized co-condensed silica particles with a nitrosating agent to provide the S-nitrosothiol-functionalized co-condensed silica particles
Data Source
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AI summary
Provided according to some embodiments of the invention are methods of forming co-condensed silica particles. In some embodiments, the methods include reacting a thiol-containing silane and a backbone alkoxysilane in a reaction solution that comprises water to form thiol-functionalized co-condensed silica particles, wherein the thiol-functionalized co-condensed silica particles include a polysiloxane matrix and at least some of thiol groups are present within the polysiloxane matrix; and reacting the thiol-functionalized co-condensed silica particles with a nitrosating agent to provide the S-nitrosothiol-functionalized co-condensed silica particles. In some embodiments, provided are S-nitrosothiol-functionalized co-condensed silica particles.