Zwitterionic Nanoparticle Contrast Agents for Renal Clearance
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Solution Overview
Problem
Current small molecule-based diagnostic contrast agents for imaging, such as X-ray/CT and MRI, face issues like short blood circulation time, high viscosity, high osmolality, renal complications, and difficulty in targeting disease sites, necessitating the development of nanoparticle-based contrast agents with improved renal clearance and reduced toxicity.
Innovation Solution
Nanoparticles with a silica-free core and a shell comprising silane-functionalized zwitterionic moieties are developed, which enhance imaging characteristics by providing improved blood half-life, reduced toxicity, and efficient renal clearance, while maintaining stability and biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If small molecule contrast agents are used, then imaging function is achieved, but blood circulation time is short and renal toxicity occurs
Solution Approach 1:
The patent changes the fundamental parameter of contrast agent size from small molecule scale to nanoparticle scale (5-50 nm diameter). This size transformation extends blood circulation time from minutes to hours while enabling renal clearance, thereby resolving the contradiction between prolonged circulation and renal toxicity through optimal size selection
Solution Approach 2:
The patent employs composite nanoparticle structures consisting of inorganic cores (iron oxide, tantalum oxide, or calcium carbonate) coated with organic shell materials (silane-functionalized zwitterionic moieties). This composite architecture provides both extended circulation time and reduced renal toxicity by combining the advantages of different materials in a synergistic system
2Duration of action of moving object
If nanoparticle size is increased to extend blood half-life, then circulation time improves, but renal clearance ability decreases
Solution Approach 1:
The patent identifies and exploits the critical size parameter window of 5-50 nm diameter, where nanoparticles are large enough to avoid rapid renal filtration (prolonging half-life) but small enough to eventually be cleared by renal filtration. This precise parameter optimization resolves the contradiction between extended circulation and maintained clearance ability
3Stability of the object's composition
If silica coating is added to nanoparticle core, then stability improves, but renal clearance is hindered
Solution Approach 1:
The patent changes the material composition parameter of the shell from silica-based coatings to silane-functionalized zwitterionic moieties. This material substitution maintains nanoparticle stability through strong core-shell bonding while preserving renal clearance ability, as the zwitterionic shell does not interfere with glomerular filtration unlike silica coatings
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 nanoparticles demonstrate enhanced imaging performance, including robust synthesis, reduced cost, and increased blood half-life, with minimal retention in the body, addressing the limitations of small molecule agents and offering improved safety and efficacy.
Implementation Method 1
The silane functionalized moieties are bound to the core at the core surface without any intervening silica layer
Data Source
AI summary
Nanoparticles (10) functionalized with at least one zwitterionic moiety, and compositions comprising said nanoparticles are provided. The nanoparticles (10) have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle (10) comprises a core (20), having a core surface (30) essentially free of silica, and a shell (40) attached to the core surface (30). The shell (40) comprises at least one silane- functionalized zwitterionic moiety. Further, methods of making said nanoparticles and methods of their use as diagnostic agents are provided.