Reverse Nanoassemblies for Multimodal Bioimaging

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Solution Overview

Problem

Current bimodal nanoparticles for dual bioimaging and therapy face issues such as emission quenching, low payload, rapid clearance, and instability in biological media, leading to reduced performance and specificity in targeting organs and malignant cells.

Innovation Solution

Development of nanoassemblies with a matrix-free organic fluorescent core surrounded by superparamagnetic nanoparticles, stabilized by a polymer coating to enhance colloidal stability and prevent aggregation, allowing for improved fluorescence retention and magnetic response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If iron oxide nanoparticles are coated with organic fluorescent units to create bimodal nanoparticles, then fluorescence and magnetism are combined for dual bioimaging, but emission quenching occurs due to electron transfer from magnetic nanoparticles to luminophores

Engineering Contradiction:
Improvedual bioimaging capabilityVSAvoidemission quenching
Core Design Contradiction:
Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent inverts the conventional core-shell architecture by placing fluorescent organic units in the core and iron oxide nanoparticles on the periphery. This reverse arrangement prevents electron transfer from magnetic nanoparticles to luminophores, thereby eliminating emission quenching while preserving dual bioimaging capability through fluorescent and magnetic resonance imaging modalities

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent introduces a polymer coating as an intermediary layer between the fluorescent core and magnetic nanoparticle periphery. This polymer shell acts as a physical barrier that separates the two components, preventing direct electron transfer while maintaining structural integrity and enabling dual imaging functionality

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If high doses of bimodal nanoparticles are used to compensate for low payload of fluorescent and magnetic active units, then sufficient signal intensity is achieved, but cytotoxicity increases and targeting specificity decreases

Engineering Contradiction:
Improvesignal intensityVSAvoidcytotoxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent creates a composite nanoassembly where fluorescent organic units and iron oxide nanoparticles are integrated in a reverse core-shell structure. This composite design maximizes the payload density of both active units within a single nanoparticle, enabling high signal intensity at low doses and reducing cytotoxicity while improving targeting specificity through functionalized surface ligands

Inventive Principle:
Principle #40Composite materials

3Stability of the object's composition

If conventional core-shell structures with magnetic core and fluorescent shell are used, then structural stability is achieved, but electron transfer effects cause fluorescence quenching and the structure requires encapsulation in silica or latex matrices

Engineering Contradiction:
Improvestructural stabilityVSAvoidencapsulation requirement
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent inverts the conventional core-shell architecture to create a reverse structure with fluorescent core and magnetic periphery. This inversion eliminates the need for additional silica or latex encapsulation layers because the reverse arrangement inherently prevents electron transfer quenching, simplifying the overall structure while maintaining stability

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent extracts and eliminates the requirement for complex silica or latex encapsulation matrices by using the reverse core-shell architecture. The inverted structure with polymer coating provides sufficient stability and protection without needing additional encapsulation layers, reducing device complexity

Inventive Principle:
Principle #2Taking out (Extraction)

4Adaptability or versatility

If bimodal nanoparticles are used for deep tissue imaging and remote mass transfer, then magnetic properties enable these functions, but fluorescence sensitivity to biological surroundings causes emission quenching or color shift

Engineering Contradiction:
Improvedeep tissue imaging capabilityVSAvoidfluorescence signal accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent inverts the core-shell architecture to place fluorescent units in the core protected from biological surroundings, while positioning magnetic nanoparticles on the periphery. This reverse arrangement shields the fluorescence-emitting units from quenching by biological molecules (proteins, lipids, ions) while maintaining magnetic resonance imaging capability for deep tissue imaging and remote targeting

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent employs a polymer coating shell that encapsulates the fluorescent core, creating a protective barrier between the luminophores and the biological environment. This flexible polymer shell prevents direct interaction between fluorescent units and biological molecules that would cause quenching or color shifts, while allowing magnetic nanoparticles on the periphery to interact with external magnetic fields for deep tissue imaging

Inventive Principle:
Principle #30Flexible shells and thin films

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 nanoassemblies provide stable fluorescence and magnetic signals, maintaining colloidal stability and preventing aggregation, enabling effective multimodal imaging and therapy while minimizing cytotoxicity and improving targeting specificity.

Implementation Method 1

at least one polymer adsorbed at the surface of the nanoassembly

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

Positioning magnetic nanoparticles on the periphery creates a charged shell structure which acts as a repelling electrostatic barrier

Methodology Applied
Scientific EffectElectrostatic repulsion: Ion Repulsion/Attraction

Implementation Method 3

magnetic nanoparticles, which are selected from the group consisting of γ-Fe2O3, Fe3O4, CoFe2O4, MnFe2O4, CuFe2O4, NiFe2O4

Methodology Applied
Scientific EffectSuperparamagnetism: Superparamagnetism

Implementation Method 4

an organic fluorescent inner core comprising fluorescent organic molecules

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3119438B1Magnetic and fluorescent reverse nanoassemblies
Publication Date: 2021.09.22 UNIV DE NANTES
  • EP3119438B1 patent drawingFigure 1~2
  • EP3119438B1 patent drawingFigure 3~4
  • EP3119438B1 patent drawingFigure 5~6

AI summary

The present invention relates to magnetic and fluorescent nanoassemblies having reverse architectures. Especially, the nanoassemblies of the invention comprise an organic fluorescent inner core and magnetic nanoparticles contacting the surface of the fluorescent core. The nanoassemblies of the invention may further be coated by a polymer adsorbed at its surface, said polymer being optionally functionalized. The invention further relates to a process for manufacturing the nanoassemblies of the invention. The invention is also directed to the use of the nanoassemblies of the invention, especially for multimodal imaging; in vitro and/or in vivo diagnostics through multimodal imaging; ex vivo sensing and/or extraction; and/or therapy.