Up-converting Nanoparticle Liposomes for Deep Tumor PDT

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Solution Overview

Problem

Current photodynamic therapy methods for treating tumors face limitations due to poor penetration of activating radiation and restricted surface application, particularly with topical gel formulations containing phthalocyanines, which are ineffective for deeper tissue tumors and require immediate skin irradiation.

Innovation Solution

A combination of up-converting nanoparticles and phthalocyanine liposomes, where nanoparticles doped with Yb and Er are used to absorb infrared light, emitting a shorter wavelength for activating phthalocyanines, allowing for deeper tissue penetration and intravenous administration, enabling infrared photodynamic therapy for tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If topical gel formulation with phthalocyanine is used, then surface application is enabled, but penetration depth of activating radiation is limited

Engineering Contradiction:

Improvesurface application areaVSAvoidpenetration depth of radiation

Core Design Contradiction:

Area of stationary objectVSLength of stationary object

Solution Approach 1:

Up-converting nanoparticles are introduced as an intermediary substance that absorbs infrared light (which penetrates deep into tissue) and converts it to visible light wavelengths that can activate phthalocyanine. This mediator enables deep tissue PDT by bridging the gap between infrared light penetration and phthalocyanine activation requirements

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the wavelength parameter of the activating light from visible range (670 nm) to infrared range, which fundamentally improves tissue penetration depth. The up-converting nanoparticles enable this parameter change by converting infrared photons to visible photons that activate phthalocyanine

Inventive Principle:

Principle #35Parameter changes

2Length of stationary object

If infrared light is used for activation, then tissue penetration depth is improved, but phthalocyanine activation efficiency decreases

Engineering Contradiction:

Improvetissue penetration depthVSAvoidphthalocyanine activation efficiency

Core Design Contradiction:

Length of stationary objectVSReliability

Solution Approach 1:

Up-converting nanoparticles serve as a light converter that absorbs infrared light and emits visible light. This intermediary conversion process allows the system to use infrared light for deep penetration while maintaining phthalocyanine activation efficiency through the emitted visible light

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite system combining up-converting nanoparticles with phthalocyanine, where the nanoparticle component provides infrared absorption and visible light emission, while the phthalocyanine component provides the photodynamic therapy function. This composite approach enables both deep penetration and efficient activation

Inventive Principle:

Principle #40Composite materials

3Ease of operation

If topical gel formulation is used, then surface tumor treatment is enabled, but treatment of deep-seated tumors is restricted

Engineering Contradiction:

Improvesurface application simplicityVSAvoidtreatment depth range

Core Design Contradiction:

Ease of operationVSAdaptability or versatility

Solution Approach 1:

The invention changes the administration route from topical application to intravenous injection, and changes the light wavelength from visible to infrared. These parameter changes enable the system to treat deep-seated tumors while maintaining ease of administration through simple intravenous injection followed by infrared light irradiation

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

This approach allows for quicker tumor accumulation and effective treatment of deep-seated tumors with infrared light, expanding treatment indications and demonstrating significant disintegration effects and remission in preclinical tests.

Implementation Method 1

nanoparticles doped with Yb and Er are used to absorb infrared light, emitting a shorter wavelength for activating phthalocyanines

Methodology Applied

Scientific EffectLight up-conversion: Photoluminescence

Implementation Method 2

The photodynamic therapy (PDT) used for the treatment of tissue tumours is based on the process where an active substance is accumulated in a tumour tissue due to the higher demands of the tumour tissue for nourishment. The tumour tissue is in some cases quite well perfused, interwoven with fenestrated capillaries and therefore, all substances get to it easier and quickly through the vascular tree

Methodology Applied

Scientific EffectEnhanced permeation and retention: Permeation

Implementation Method 3

After the active substance is applied and concentrates in the tumour, PDT is used to irradiate the tumour tissue with light of certain wavelength

Methodology Applied

Scientific EffectPhotodynamic therapy: Photo-oxidation

Data Source

PatentEP3697385B1Liposome drug form with light-converting nanoparticles, a method of its preparation and use

Publication Date: 2021.11.10 INST OF PHYSIOLOGY CAS

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AI summary

A liposome drug form is applied intravenously and subsequently irradiated with laser at wavelength in the infrared spectrum which passes deep into tissue. Nanoparticles convert the infrared radiation to wavelength of 670 nm which activates phtalocyanines and subsequently causes disintegration of the tumour tissue.