Mitochondrial Targeting Nanoparticles with Size and Charge Optimization

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Solution Overview

Problem

Current methods face challenges in delivering drugs effectively to mitochondria while avoiding toxicity, as existing technologies struggle to target and accumulate therapeutic agents within these organelles efficiently.

Innovation Solution

Nanoparticles with a hydrophobic core and hydrophilic layer, incorporating a mitochondrial targeting moiety, are designed to have a diameter of 200 nanometers or less and a zeta potential of 0 mV or greater, allowing for targeted delivery of therapeutic and diagnostic agents directly to mitochondria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nanoparticles with diameter greater than 200 nanometers are used, then the nanoparticle structure is more stable and easier to manufacture, but the ability to accumulate in mitochondria is reduced

Engineering Contradiction:
Improvenanoparticle stabilityVSAvoidmitochondrial accumulation
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by optimizing the nanoparticle diameter to 200 nanometers or less, which is a specific parameter threshold that enables mitochondrial accumulation while maintaining structural stability. This size parameter change resolves the contradiction between stability and accumulation capability.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If nanoparticles with negative zeta potential are used, then the nanoparticle formulation is simpler, but the ability to accumulate in mitochondria is reduced

Engineering Contradiction:
Improveformulation simplicityVSAvoidmitochondrial accumulation
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the zeta potential parameter from negative to positive (0 mV or greater), which fundamentally alters the nanoparticle's interaction with mitochondrial membranes. This parameter change enables enhanced mitochondrial accumulation while maintaining formulation feasibility.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If higher concentration of agents is delivered to mitochondria, then the therapeutic efficacy is improved, but the toxicity to other cellular locations increases

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidcellular toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The nanoparticle acts as an intermediary delivery vehicle that selectively transports therapeutic agents to mitochondria. By using the nanoparticle as a mediator with specific size and charge properties, the patent achieves targeted delivery that concentrates agents at the mitochondrial location while minimizing exposure and toxicity to other cellular compartments.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies local quality by creating highly concentrated agent delivery specifically at the mitochondrial location rather than uniform distribution throughout the cell. This localized concentration approach enhances therapeutic efficacy at the target site while reducing harmful effects in other cellular regions.

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

This approach enhances the concentration of agents within mitochondria, improving efficacy while minimizing side effects and toxicity, and is effective for treating diseases associated with mitochondrial dysfunction such as cancer, neurodegenerative diseases, and obesity.

Implementation Method 1

Nanoparticles having a zeta potential of about 0 or greater are found to more readily accumulate in the mitochondria than nanoparticles having zeta potentials of less than about zero

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

nanoparticles having diameters of about 200 nanometers or less are found to more readily accumulate in the mitochondria than nanoparticles having diameters greater than about 200 nanometers

Methodology Applied
Scientific EffectSize-based accumulation: Diffusion

Data Source

PatentUS10845368B2Nanoparticles for mitochondrial trafficking of agents
Publication Date: 2020.11.24 UNIVERSITY OF GEORGIA RESEARCH FOUNDATION INC
  • US10845368B2 patent drawing
  • US10845368B2 patent drawing
  • US10845368B2 patent drawing

AI summary

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.