Targeted Nanoparticles Using Boronic Acid Linkages

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Solution Overview

Problem

Current methods for delivering compounds of interest to cells, tissues, and organisms face challenges in targeting specific locations and maintaining stability, leading to inefficiencies and degradation of therapeutic agents.

Innovation Solution

Development of nanoparticles comprising polymers with polyol and boronic acid groups that form reversible covalent linkages, allowing for targeted and controlled delivery of compounds by presenting the boronic acid to the environment and using a single targeting ligand for enhanced specificity and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional delivery methods are used, then delivery can be achieved, but targeting specificity and stability are poor leading to degradation of therapeutic agents

Engineering Contradiction:

Improvestability of therapeutic agentVSAvoidcomplexity of delivery system

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs composite nanoparticle structures combining polymer shells with embedded therapeutic agents and targeting ligands. This composite approach provides both protection/stability for the therapeutic agent and integrated targeting functionality, resolving the contradiction between reliability and manufacturing complexity by combining multiple functions into a single engineered system.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The nanoparticle delivery system is segmented into distinct functional components: a protective polymer shell, embedded therapeutic agents, and surface-presented targeting ligands. This segmentation allows each component to be optimized independently while working together to provide stable, targeted delivery, addressing both reliability and ease of manufacture considerations.

Inventive Principle:

Principle #1Segmentation

2Reliability

If multiple targeting ligands are used to enhance targeting, then specificity improves, but cost increases due to use of costly antibodies

Engineering Contradiction:

Improvetargeting specificityVSAvoidcost of antibodies

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent employs PEGylated boronic acid moieties that serve multiple functions: they provide steric stabilization, enable reversible covalent bonding to polyol-containing targets, and can be conjugated to various targeting ligands. This multi-functionality reduces the need for multiple different antibody types, lowering costs while maintaining targeting specificity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes reversible covalent bonding parameters between boronic acid and polyol groups, allowing dynamic control of ligand presentation. This parameter change approach enables cost-effective optimization of targeting specificity by adjusting bonding conditions rather than requiring multiple expensive antibody variants.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If nanoparticles present boronic acid to external environment, then reversible covalent binding occurs enhancing stability, but device complexity increases

Engineering Contradiction:

Improvestability of nanoparticleVSAvoidcomplexity of nanoparticle structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The PEGylated boronic acid acts as an intermediary between the nanoparticle core and the external environment. It provides reversible covalent bonding capability that enhances nanoparticle stability while the PEG spacer simplifies the overall structure by providing a standardized link, reducing device complexity despite the added functionality.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Productivity

If conventional delivery systems are used, then delivery occurs, but nonspecific binding increases reducing delivery efficiency

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidnonsspecific binding

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The nanoparticle employs local quality differentiation with hydrophilic PEG chains on the outer surface that resist nonspecific binding, while boronic acid groups are positioned to specifically interact with polyol-containing targets. This spatial arrangement of different chemical properties reduces harmful nonspecific binding while maintaining high delivery efficiency to intended targets.

Inventive Principle:

Principle #3Local quality

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 provide effective, specific, and controlled delivery of compounds, reducing nonspecific binding and degradation, and can release therapeutic agents at desired rates and locations, improving therapeutic efficacy and reducing the need for costly antibodies.

Implementation Method 1

a polymer containing a boronic acid and a polymer containing a polyol capable of reciprocal binding through a reversible covalent linkage

Methodology Applied

Scientific EffectReversible covalent linkage: Chemical Bonding

Data Source

PatentUS11285212B2Targeted nanoparticles

Publication Date: 2022.03.29 CALIFORNIA INST OF TECH

AI summary

Described herein are carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a nitroboronic boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing the nitroboronic acid to an environment external to the nanoparticle. Targeted versions of the described nanoparticles are also described, as are related compositions, methods and systems.