Lanthanide Nanoparticles for Tumor Radiation Absorption

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Solution Overview

Problem

Current radio-sensitizers for cancer treatment, particularly those based on molecular compounds and metallic nanoparticles, face challenges in achieving selective accumulation in tumors over healthy tissues, leading to non-specific distribution and toxicity concerns.

Innovation Solution

Development of nanoparticles with dimensions between 1 and 50 nm, composed of lanthanide oxides or oxohydroxides, optionally coated with polysiloxane, which can accumulate preferentially in tumors due to their small size and stability, enhancing radiation absorption and minimizing non-specific uptake.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If molecular compounds with heavy elements are used as radio-sensitizers, then radiation absorption is enhanced, but the agents are rapidly eliminated and diffuse extravascularly, preventing sufficient concentration in tumors

Engineering Contradiction:
Improveradiation absorptionVSAvoidconcentration in tumor
Core Design Contradiction:
Use of energy by moving objectVSQuantity of substance

Solution Approach 1:

The patent changes the physical form of the radio-sensitizing agent from molecular compounds to nanoparticles with controlled size (1-50 nm). This parameter change fundamentally alters the pharmacokinetic properties, enabling preferential tumor accumulation through enhanced permeability and retention effect while maintaining high radiation absorption capacity due to the high atomic number elements contained in the nanoparticles.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite nanoparticle structures comprising a core of inorganic compound containing heavy elements (for radiation absorption) and a shell of biocompatible material (for stability and targeting). This composite structure combines the radiosensitizing capability of heavy elements with the favorable biodistribution properties of nanoparticle carriers, resolving the contradiction between radiation absorption and tumor concentration.

Inventive Principle:
Principle #40Composite materials

2Use of energy by moving object

If finely divided solids like metal powders are used as radio-sensitizers, then radiation absorption is improved, but mobility and dispersion become uncontrolled problems

Engineering Contradiction:
Improveradiation absorptionVSAvoidmobility and dispersion control
Core Design Contradiction:
Use of energy by moving objectVSEase of operation

Solution Approach 1:

The patent coats the metal or metal oxide nanoparticle cores with thin film shells of biocompatible materials. These shells provide colloidal stability, prevent uncontrolled aggregation and dispersion, while maintaining the radiosensitizing properties of the core. The shell acts as a protective layer that controls the interaction between the nanoparticle and the biological environment, resolving the mobility and dispersion control issues.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

By creating composite structures with a metal/metal oxide core and a biocompatible shell, the patent combines the high radiation absorption of metals with the controlled behavior of stable colloidal particles. The composite structure maintains the advantageous radiosensitizing properties while eliminating the uncontrolled mobility and dispersion problems of metal powders.

Inventive Principle:
Principle #40Composite materials

3Power

If high atomic number elements are used to increase absorbed radiation dose, then therapeutic effect is enhanced, but healthy tissues are also affected and toxicity increases

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtoxicity to healthy tissue
Core Design Contradiction:
PowerVSObject-affected harmful factors

Solution Approach 1:

The patent segments the radio-sensitizing function into discrete nanoparticles that can be independently controlled and targeted. By using nanoparticles instead of soluble molecular compounds, the system achieves spatial segmentation of the radiosensitizing effect, concentrating it in tumor regions while minimizing exposure of healthy tissues. This segmentation enables selective accumulation through passive targeting mechanisms.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements local quality by creating nanoparticles with heterogeneous structure - a radiosensitizing core and a biocompatible shell - where different parts of the nanoparticle serve different functions. Additionally, the nanoparticles achieve local concentration in tumor tissues through the enhanced permeability and retention effect, creating a local quality difference between tumor and healthy tissue that reduces systemic toxicity while maintaining therapeutic efficacy.

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

These nanoparticles enable a higher concentration of radio-sensitizing agents in tumors, increasing the therapeutic efficacy of X or gamma irradiation while reducing toxicity and cost compared to traditional methods, with improved biodistribution and longer residence time in the body.

Implementation Method 1

The use of small particles makes it possible to hope for good dispersion of the radio-sensitizers. On the other hand, the high density coupled with the strong atomic number of the element makes it possible to hope for good absorption of radiation.

Methodology Applied
Scientific EffectPhotoelectric absorption: Absorption (EM radiation)

Implementation Method 2

A greater part of the irradiated energy is then absorbed and deposited locally around the radio-sensitizers and can produce secondary electrons, Auger electrons, Compton electrons, ionizations, photons, free radicals for example

Methodology Applied
Scientific EffectCompton scattering: Compton Scattering

Implementation Method 3

A greater part of the irradiated energy is then absorbed and deposited locally around the radio-sensitizers and can produce secondary electrons, Auger electrons, Compton electrons, ionizations, photons, free radicals for example

Methodology Applied
Scientific EffectAuger effect: Auger Effect

Implementation Method 4

nanoparticles whose dimensions are between 1 and 50 nm, which either consist exclusively of at least one inorganic compound or consist of a core comprising at least one inorganic compound and a shell comprising at least one organic compound or mixed organic/inorganic compound

Methodology Applied
Scientific EffectColloidal stabilization: Colloid

Data Source

PatentEP2200659B1Use of lanthanide-based nanoparticles as radiosensitizing agents
Publication Date: 2015.07.22 NANO H
  • EP2200659B1 patent drawingFigure 1~3
  • EP2200659B1 patent drawingFigure 4~5b
  • EP2200659B1 patent drawingFigure 6~8

AI summary

The invention relates to the use of nanoparticles having dimensions between 1 and 50 nm, at least one part of which is constituted of at least one oxide and/or one oxyhydroxide of at least lanthanide, said nanoparticles being: - either constituted of at least one oxide and/or one oxyhydroxide of at least one lanthanide, - or in the form of nanoparticles comprising an oxyhydroxide core of at least one lanthanide, and a coating constituted of a polysiloxane, optionally with organic molecules grafted to the surface or included within it, as a radiosensitizing agent in the manufacture of an injectable composition intended for improving the effectiveness of the treatment of a tumour by X-ray or gamma irradiation. It also relates to nanoparticles that are particularly suitable for the above use, constituted of a core constituted of at least one oxide and/or one oxyhydroxide of at least one lanthanide and of a polysiloxane coating comprising 1 to 5 silicons per lanthanide and of which at least 10% of the silicon atoms are linked to hydrophilic organic molecules having molar masses of less than 450 g/mol.