Gold Nanoparticle Encapsulation in Biodegradable Polymer Particles

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Solution Overview

Problem

Multifunctional gold nanoparticles used in cancer treatment have a short plasma half-life, leading to rapid renal clearance and reduced accumulation in tumor zones, which hampers their radiosensitizing and imaging potential, and existing encapsulation methods result in low yield, large particle size, and polydispersity.

Innovation Solution

Encapsulating gold nanoparticles in biodegradable polymer particles using a polycation with a positive charge over a wide pH range, facilitating electrostatic trapping and achieving high encapsulation yields and uniform particle sizes, thereby extending plasma half-life and improving tumor accumulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multifunctional gold nanoparticles are used for cancer treatment, then radiosensitizing and imaging properties are improved, but plasma half-life is shortened leading to rapid renal clearance

Engineering Contradiction:

Improveradiosensitizing and imaging propertiesVSAvoidplasma half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent encapsulates multifunctional gold nanoparticles within biodegradable polymer particles, creating a nested structure where the gold nanoparticles (6-7 nm) are contained inside larger polymer particles (100-200 nm). This nesting allows the inner gold nanoparticles to maintain their radiosensitizing and imaging properties while the outer polymer layer extends plasma half-life by reducing renal clearance

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent creates a composite particulate structure combining biodegradable polymer material with multifunctional gold nanoparticles. The polymer matrix provides extended circulation time and controlled degradation, while the gold nanoparticle core delivers radiosensitizing and imaging functions, achieving synergistic properties that resolve the contradiction between short half-life and therapeutic efficacy

Inventive Principle:

Principle #40Composite materials

2Duration of action of moving object

If gold nanoparticles are encapsulated in larger particles to extend circulation time, then plasma half-life is improved, but renal elimination is reduced

Engineering Contradiction:

Improveplasma half-lifeVSAvoidrenal elimination

Core Design Contradiction:

Duration of action of moving objectVSLoss of substance

Solution Approach 1:

The patent employs a dynamic, time-dependent behavior where the polymer particles maintain their larger size (100-200 nm) during circulation to extend plasma half-life, then degrade in vivo to release the gold nanoparticles for renal elimination. This dynamic transformation resolves the contradiction by having different size states at different time points

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent utilizes parameter changes in the polymer particle size over time - starting at 100-200 nm for extended circulation, then degrading to release 6-7 nm gold nanoparticles for renal clearance. The biodegradability parameter of the polymer enables this size transformation, simultaneously achieving extended half-life and maintained elimination capability

Inventive Principle:

Principle #35Parameter changes

3Duration of action of moving object

If existing encapsulation methods are used for gold nanoparticles, then plasma half-life is extended, but encapsulation yield is low and particle size is large with polydispersity

Engineering Contradiction:

Improveplasma half-lifeVSAvoidencapsulation yield and particle size uniformity

Core Design Contradiction:

Duration of action of moving objectVSManufacturing precision

Solution Approach 1:

The patent uses a specific polycation as an intermediary agent during encapsulation that facilitates uniform distribution and trapping of gold nanoparticles within polymer particles. This intermediary enables high encapsulation yield (>90%) and narrow size distribution (PDI < 0.2), resolving the contradiction between extended circulation time and manufacturing precision

Inventive Principle:

Principle #24Intermediary (Mediator)

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 approach results in gold nanoparticles with a prolonged plasma half-life, enhanced accumulation in tumors, and efficient renal elimination, while maintaining radiosensitizing and imaging properties, and allows for the co-encapsulation of chemotherapeutic agents, improving the effectiveness of image-guided radiotherapy and chemotherapy.

Implementation Method 1

using a polycation having a positive charge over a wide pH range, facilitating electrostatic trapping

Methodology Applied

Scientific EffectElectrostatic trapping: Electrostatic Induction

Data Source

PatentUS20220257801A1Particulate structures made from gold nanoparticles, methods for preparing same and uses thereof for treating solid tumours

Publication Date: 2022.08.18 UNIVERSITE DE FRANCHE COMTE

AI summary

A particulate structure that includes a/ a biodegradable polymer particle, b/ gold nanoparticles covered on their surface with macrocyclic chelators complexing at least one ion of interest and/or a radionuclide for medical imaging, c/ a polycation having a positive charge over a pH range from 5 to 11, the gold nanoparticles b/ being encapsulated in the polymer particle a/ and/or adsorbed at the surface of the polymer particle a/. Also, a method for preparing the particulate structures. Further, the use of the particulate structures for radiotherapy or chemotherapy in the context of cancer treatment.