Zwitterionic Nanoparticle Contrast Agents for Renal Clearance

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Solution Overview

Problem

Current small molecule-based diagnostic contrast agents for imaging have limitations such as short blood circulation time, high viscosity, high osmolality, and renal complications, necessitating the development of nanoparticle-based agents with improved renal clearance and reduced toxicity.

Innovation Solution

Nanoparticles with a core surface essentially free of silica and a shell comprising silane-functionalized zwitterionic moieties, such as tantalum oxide or superparamagnetic iron oxide cores, are developed to enhance imaging characteristics, including increased blood half-life and decreased toxicity.

Engineering Contradictions & Design Principles

VSEngineering 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

Engineering Contradiction:

Improveblood circulation timeVSAvoidrenal toxicity

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical state and size parameters by transitioning from small molecule contrast agents to nanoparticle-based agents with specific size ranges (e.g., 2-10 nm diameter). This parameter change extends blood circulation time while the zwitterionic surface functionalization modifies chemical properties to reduce renal toxicity and improve biocompatibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite nanoparticle structures consisting of a core material (providing contrast function) combined with a zwitterionic shell or surface coating. This composite structure integrates the imaging functionality with improved circulation properties and reduced toxicity, resolving the contradiction between effective imaging and harmful renal effects

Inventive Principle:

Principle #40Composite materials

2Duration of action of moving object

If nanoparticle size is increased, then blood half-life is increased, but retention in body increases and renal clearance decreases

Engineering Contradiction:

Improveblood half-lifeVSAvoidrenal clearance

Core Design Contradiction:

Duration of action of moving objectVSLoss of substance

Solution Approach 1:

The patent optimizes the nanoparticle size parameter within a specific range (2-10 nm diameter) to achieve the optimal balance between extended blood half-life and maintainable renal clearance. This precise parameter control allows the particles to circulate longer while still being efficiently cleared by renal filtration

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent designs nanoparticles with size and surface properties that mimic the filtration characteristics of small molecules, allowing them to be cleared by renal filtration mechanisms similar to endogenous substances, thereby maintaining efficient renal clearance despite the nanoparticle format

Inventive Principle:

Principle #26Copying

Data Source

PatentUS8574549B2Nanoparticle contrast agents for diagnostic imaging

Publication Date: 2013.11.05 GE HEALTHCARE LTD

AI summary

Compositions of nanoparticles functionalized with at least one zwitterionic moiety, methods for making a plurality of nanoparticles, and methods of their use as diagnostic agents are provided. The nanoparticles have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle comprises a core, having a core surface essentially free of silica, and a shell attached to the core surface. The shell comprises at least one silane-functionalized zwitterionic moiety.