pH-Sensitive Metal Nanoparticles for Selective Cancer Cell Targeting

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current metal and metal-coated nanoparticles for photothermal therapy face challenges in selectively detecting and targeting cancer cells due to limitations in developing effective biological ligands for specific cancer cell detection and conjugation.

Innovation Solution

Development of pH-sensitive metal or metal-coated nanoparticles with compounds that change charge in response to pH, allowing them to aggregate in acidic environments, such as cancer cells, and absorb longer wavelengths of light for targeted photothermal therapy, enabling selective destruction of cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional metal nanoparticles are used for photothermal therapy, then they can absorb light and generate heat, but they cannot selectively target cancer cells due to lack of pH sensitivity

Engineering Contradiction:
Improveselectivity for cancer cellsVSAvoidpH-responsive aggregation capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by utilizing the pH-dependent charge state of amino acid compounds on nanoparticle surfaces. At acidic pH (cancer cell environment), the compounds become positively charged, causing nanoparticle aggregation. At neutral pH (normal cells), they remain negatively charged and dispersed. This parameter change enables selective cancer cell targeting through pH-responsive aggregation behavior.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite nanoparticles by coating metal cores with pH-sensitive amino acid compounds (lysine, arginine, or histidine). This composite structure combines the light-absorbing and heat-generating properties of metal nanoparticles with the pH-responsive targeting capability of amino acid coatings, achieving both photothermal therapy function and cancer cell selectivity.

Inventive Principle:
Principle #40Composite materials

2Reliability

If nanoparticles aggregate in acidic environments, then they can selectively target cancer cells, but their light absorption wavelength shifts which may affect penetration depth

Engineering Contradiction:
Improvecancer cell targeting accuracyVSAvoidlight absorption wavelength
Core Design Contradiction:
ReliabilityVSLength of stationary object

Solution Approach 1:

The patent accepts and utilizes the wavelength shift as a consequence of pH-induced aggregation. The aggregation at acidic pH causes red-shift in light absorption to longer wavelengths (near-infrared region), which actually improves tissue penetration depth. This parameter change is leveraged to enhance both targeting accuracy and penetration capability simultaneously.

Inventive Principle:
Principle #35Parameter changes

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 pH-sensitive nanoparticles effectively aggregate in cancer cells, shifting their light absorption to longer wavelengths, allowing for deep tissue penetration and selective cancer cell destruction with minimal impact on normal cells, thereby enhancing the applicability and selectivity of photothermal therapy.

Implementation Method 1

said nanoparticles have compounds on their surface, wherein the charge of the compound changes depending on pH

Methodology Applied
Scientific EffectpH-dependent charge change: Ionisation

Implementation Method 2

the charge of the compound changes depending on pH... aggregate in acidic environments

Methodology Applied
Scientific EffectElectrostatic attraction: Ion Repulsion/Attraction

Implementation Method 3

The light collected on the surface of gold nanoparticles is emitted by various processes, including electron-lattice vibrations, and electron-electron scattering, with the concomitant production of heat

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 4

metal nanoparticles have been becoming popular because of the possibility of their being used in photothermal therapy thanks to the light-harvesting effect thereof

Methodology Applied
Scientific EffectPhotothermal conversion: Photoacoustic Effect

Implementation Method 5

Surface plasmons are the collective oscillations of free electrons of a metal surface on which light is incident, which take place due to resonance with electromagnetic waves of specific energy

Methodology Applied
Scientific EffectSurface plasmon resonance: Resonance

Data Source

PatentEP2308799B1Ph sensitive metal nanoparticle and preparation method
Publication Date: 2017.11.08 POSTECH ACADEMY INDUSTRY FOUNDATION
  • EP2308799B1 patent drawingFigure 1
  • EP2308799B1 patent drawingFigure 2
  • EP2308799B1 patent drawingFigure 3

AI summary

The present invention relates to a pH sensitive particle, a method of preparation thereof, and a use thereof. More particularly, the invention provides a pH sensitive metal nanoparticle and its use for medical treatment utilizing cell necrosis during photothermal therapy. The pH sensitive metal nanoparticle based on this invention consists of a pH sensitive ligand compound whose charge changes depending on the pH of the metal nanoparticle. The particle can be collected in cells, such as cancer cells which present an abnormal pH environment. The pH sensitive metal nanoparticle based on this invention can induce cell death through a photothermal procedure after aggregation. Therefore, the invention enables medical treatment using cell necrosis for e.g. cancer treatment.