Functionalized Core-Shell Nanogel for Dual LPS and Cytokine Scavenging
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Solution Overview
Problem
Current treatments for sepsis, a life-threatening hyperinflammatory syndrome, have unacceptably high mortality rates due to the lack of effective methods for simultaneously neutralizing lipopolysaccharides (LPS) and cytokines, which trigger systemic inflammation.
Innovation Solution
A biomolecule-binding nanogel composition comprising crosslinked hydrogel nanoparticles with dendritic telodendrimers functionalized with hydrophobic and charged moieties, polymerized with a PEG chain, is developed to selectively capture LPS and cytokines, providing a size-exclusive network for effective immune modulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cationic amphiphilic small molecules, peptides, and antibodies are used for LPS attenuation, then LPS binding capability is improved, but mortality reduction efficacy is insufficient
Solution Approach 1:
The patent combines LPS binding capability with cytokine scavenging capability into a single nanogel system. The nanogel simultaneously binds LPS through its amphiphilic structure and scavenges cytokines through its porous network, achieving dual functionality that resolves the insufficiency of single-function therapies in reducing mortality
Solution Approach 2:
The nanogel is constructed as a composite material with specific hydrophobic and hydrophilic domains. The hydrophobic regions bind LPS while the hydrophilic porous network traps cytokines, creating a composite structure that achieves both LPS attenuation and cytokine removal for improved mortality reduction efficacy
2Quantity of substance
If anti-cytokine therapies are used, then cytokine levels are reduced, but simultaneous LPS attenuation is not achieved
Solution Approach 1:
The nanogel is designed as a universal therapeutic agent that performs multiple functions: it scavenges cytokines through its porous structure and simultaneously binds LPS through its amphiphilic moieties. This multi-functional design allows a single therapy to address both cytokine overload and LPS presence, achieving versatility that single-function anti-cytokine therapies lack
3Object-affected harmful factors
If conventional LPS-attenuating therapies are used, then LPS neutralization is achieved, but cytokine removal is not accomplished
Solution Approach 1:
The nanogel merges LPS neutralization function with cytokine removal function into a single therapeutic system. The amphiphilic structure provides LPS binding while the porous network enables cytokine trapping, creating a dual-function therapy that simultaneously addresses both harmful factors without requiring separate treatments
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 nanogel effectively attenuates NF-κB activation and cytokine production in septic mouse models, improving survival rates and reducing systemic inflammation by scavenging LPS and cytokines, demonstrating potential as a novel therapeutic modality for sepsis treatment.
Implementation Method 1
dendritic functionalized telodendrimer containing a plurality of hydrophobic groups and hydrophilic charged binding moieties
Implementation Method 2
hydrophilic charged binding moieties
Implementation Method 3
the linear polyethylene glycol polymer (PEG) chain extending on the surface of the nanoparticle to protect a size-exclusive nanogel network
Implementation Method 4
nano-sized crosslinked hydrogel system... to protect a size-exclusive nanogel network
Data Source
AI summary
Sepsis is a life-threatening complication of host response to infection and tissue damages. It is characterized by the uncontrolled systemic inflammatory response. Immune modulation therapy hasn't demonstrated consistent benefit in the clinic, due to the dynamic, complex, and heterogenous immune response in sepsis. Spontaneous attenuation of a broad spectrum of septic molecules and cytokines is promising for effective sepsis treatment. Embodiments disclosed herein are directed to functionalized nano-sized hydrogel, i.e., nanogel (NG), via a one-pot precipitation polymerization using biocompatible, biodegradable monomers/crosslinkers and versatile polymerizable hybrid telodendrimer (TD) nanotraps (NTs) for effective septic molecules scavenging.