Functionalized Nanoparticles for Pathogen Trapping and Clearance
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Solution Overview
Problem
Current treatments for SARS-CoV-2 infection, such as remdesivir and convalescent plasma, have limitations including inconsistent clinical benefits and adverse effects, and there is a need for additional compositions and methods for safely and effectively treating or preventing SARS-CoV-2 and other pathogen infections.
Innovation Solution
Development of functionalized nanoparticles with a biocompatible polymer core and an outer lipid layer functionalized with pathogen-binding receptors or antibodies and phagocyte-specific ligands, which can mimic pathogen target cells, bind to pathogens, and be targeted for engulfment and clearance by macrophages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If remdesivir is used to treat severe COVID-19, then treatment options are available, but clinical benefits are inconsistent and adverse effects occur
Solution Approach 1:
The patent uses soluble ACE2 protein as a decoy that copies the natural cell surface receptor, creating a soluble version that can bind SARS-CoV-2 in circulation without requiring cellular entry, thereby avoiding the adverse effects of antiviral drugs while providing consistent therapeutic benefit
Solution Approach 2:
The soluble ACE2 acts as an intermediary molecule that intercepts the virus-antibody complex or free virus particles, preventing them from binding to actual cell receptors. This intermediary approach provides a safer alternative to direct antiviral agents like remdesivir
2Reliability
If convalescent plasma is transfused, then clinical benefits are observed, but limited availability of donor plasma and appropriate medical facilities challenges this approach
Solution Approach 1:
Instead of relying on donated plasma containing natural antibodies, the patent produces recombinant neutralizing antibodies and soluble ACE2 in bioreactors, creating an artificial but equally effective treatment that can be manufactured on demand without depending on donor availability
Solution Approach 2:
The patent transforms the treatment from a biological product dependent on human donors (convalescent plasma) to a standardized pharmaceutical product (recombinant antibodies and soluble ACE2) with controlled production parameters, enabling consistent supply and broader accessibility
3Reliability
If nanoparticles are designed to bind pathogens, then pathogen neutralization is achieved, but clearance by the immune system may be hindered
Solution Approach 1:
The patent applies different functional properties to different parts of the nanoparticle: the surface is functionalized with pathogen-binding receptors for high-affinity viral capture, while the core composition and surface charge are optimized for macrophage recognition and clearance, achieving both binding efficacy and appropriate immune clearance
Solution Approach 2:
Instead of designing nanoparticles that evade immune detection (which would prolong circulation), the patent intentionally designs them to be recognized and cleared by macrophages, inverting the conventional approach. The phagocyte-specific ligands actively recruit immune cells to clear the virus-nanoparticle complexes from circulation and infected 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 functionalized nanoparticles effectively inhibit SARS-CoV-2 infection by trapping virions and preventing cell entry, while also being safely cleared by the immune system, demonstrating a promising therapeutic approach for COVID-19 and potentially other pathogen infections.
Implementation Method 1
the outer surface of the outer layer comprises: (c) a pathogen-binding receptor and/or a pathogen-binding antibody or an antigen-binding fragment thereof
Implementation Method 2
groups that can target the functionalized nanoparticles for macrophage engulfment and clearance
Data Source
AI summary
Functionalized nanoparticles for inhibiting or preventing pathogen infections (e.g., viral or bacterial infections, such as coronavirus infections) are described. The nanoparticles comprise a biodegradable polymer core and a lipid coating layer that is functionalized with a pathogen-binding receptor (e.g., an angiotensin-converting enzyme 2 (ACE2) receptor protein) and/or a pathogen-binding antibody or an antigen-binding fragment thereof (e.g., a virus-binding antibody or an antigen-binding fragment thereof). The nanoparticles are further functionalized by a phagocyte-specific ligand, e.g., a phosphatidylserine-containing lipid included in the lipid coating layer, to promote clearance of nanoparticle-bound pathogen. Methods of using the nanoparticles to treat or prevent pathogen infections (e.g., coronavirus infections) are also described.