Reduced Nanohydrogel Composition for Stable Nucleic Acid Loading
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Solution Overview
Problem
Existing polymeric nanohydrogels (NHGs) are unstable in non-aqueous environments, irreversibly transform into films upon drying, and have negative zeta potentials that prevent nucleic acid complexation, limiting their effectiveness as drug and nucleic acid delivery systems.
Innovation Solution
A process for preparing polymeric monodispersed reduced nanohydrogels (NHGs) involving the combination of monomers, cross-linkers, and surfactants, followed by heating and reduction steps, using bis-acrylamide and polyvinylpyrrolidone, to achieve biocompatibility and positive zeta potential, enabling nucleic acid complexation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If polymeric nanohydrogels are prepared with conventional methods, then they can be formed as nanoparticles, but they are unstable in non-aqueous environments and irreversibly transform into films upon drying
Solution Approach 1:
The patent applies parameter changes by modifying the chemical composition parameters of the nanohydrogel through reduction treatment. The disulfide bonds in the polymer network are reduced to thiol groups, fundamentally changing the chemical state of the crosslinking mechanism. This parameter change enables the nanohydrogel to maintain nanoparticle morphology in non-aqueous environments and prevents irreversible film formation upon drying, while still allowing reversible aggregation controlled by redox conditions.
2Reliability
If conventional nanohydrogels are used, then they provide structural stability, but their negative zeta potential prevents complexation with nucleic acids
Solution Approach 1:
The patent changes the surface charge parameter of the nanohydrogel through reduction. The disulfide-crosslinked network is reduced to generate thiol groups on the nanoparticle surface, which fundamentally alters the zeta potential from negative to positive. This parameter change enables electrostatic attraction and complexation with negatively charged nucleic acids, while the crosslinked core structure maintains structural stability.
3Stability of the object's composition
If nanohydrogels are made highly stable, then they maintain nanoparticle properties, but they may aggregate and cause embolism risk
Solution Approach 1:
The patent introduces dynamic redox-responsive behavior to the nanohydrogel system. The thiol-disulfide exchange reactions allow the nanoparticle to dynamically adjust its aggregation state based on environmental redox conditions. In reducing environments (such as intracellular conditions), the nanoparticles remain dispersed and stable. In oxidizing environments, controlled aggregation can occur through disulfide bond formation, but this is reversible and controllable, preventing permanent embolism-causing aggregates.
4Strength
If cross-linking is increased to improve stability, then nanoparticle structure is strengthened, but cargo loading capacity may be reduced
Solution Approach 1:
The patent applies local quality by creating a heterogeneous structure where the core of the nanohydrogel contains the crosslinked polymer network for structural stability, while the surface and interstitial regions provide loading capacity for cargo molecules. The reduction process generates thiol groups primarily at the nanoparticle surface and in accessible regions, creating a gradient of crosslinking density. This allows the core to maintain structural integrity while the periphery provides ample space and functional groups for nucleic acid and drug loading.
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 resulting NHGs maintain stability in non-aqueous conditions, allow effective nucleic acid loading, and facilitate high cellular uptake, expressing endogenous or exogenous proteins without toxicity, suitable for gene therapy applications.
Implementation Method 1
performing an NHG reduction step
Implementation Method 2
releasing the NHG by dissolving the magnetic matrix in an acid
Data Source
AI summary
A process for preparing polymeric monodispersed reduced nanohydrogels (NHGs) comprises: a) combining monomers, macromonomer, a cross-linker, and a surfactant to obtain a precursor mixture; b) heating the precursor mixture to a temperature of at least 40° C.; c) adding an initiator to the precursor mixture to obtain polymeric NHG; and d) performing an NHG reduction step. Polymeric monodispersed reduced NHGs and methods of use thereof are also disclosed.