Ginseng-Derived Nanoparticles Repolarize M2 Macrophages

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Solution Overview

Problem

Current immunopotentiators, such as traditional granulocyte-macrophage colony-stimulating factor, fail to fully activate monocyte-macrophages and promote cell-mediated immune responses, and are inadequate in re-polarizing tumor-associated macrophages from M2 to M1 type, which are crucial for effective tumor treatment and immune regulation.

Innovation Solution

Ginseng-derived nanoparticles (GDNP) with a membrane structure and particle size ranging from 150 to 500 nm, produced through a specific centrifugation process, are used to activate monocyte-macrophages and re-polarize tumor-associated macrophages from M2 to M1 type by up-regulating specific surface markers and cytokines, thereby enhancing immune responses and improving the tumor microenvironment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional granulocyte-macrophage colony-stimulating factor is used, then monocyte-macrophage growth is promoted, but TLR and related immune molecules cannot be activated, thus cell-mediated immune response cannot be fully promoted

Engineering Contradiction:
Improvemonocyte-macrophage growthVSAvoidimmune response activation
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent uses a composite nanoparticle system comprising ginseng extract components (such as ginsenosides) combined with immunopotentiating agents. This composite structure allows simultaneous promotion of monocyte-macrophage growth and activation of TLR immune molecules, resolving the limitation of single-agent approaches.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the chemical and physical parameters of the immunopotentiator by formulating it as a nanoparticle with specific size (10-200 nm), surface charge, and composition ratios. These parameter changes enhance both the proliferative effect on monocytes and the activating effect on immune molecules, overcoming the trade-off between growth promotion and immune activation.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If tumor-associated macrophages (M2 type) are present in tumor microenvironment, then tumor growth and metastasis are promoted, but conversion to M1 type is needed for anti-tumor immunity

Engineering Contradiction:
Improvemacrophage populationVSAvoidtumor promotion by M2 macrophages
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent applies an inverted approach by not trying to eliminate M2 macrophages but rather converting them to M1 type through specific nanoparticle treatment. This inversion transforms the harmful M2 population into beneficial M1 cells, simultaneously maintaining macrophage quantity while eliminating their tumor-promoting effects.

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

Solution Approach 2:

The ginseng-derived nanoparticle acts as an intermediary agent that mediates the polarization transition of macrophages from M2 to M1 phenotype. The nanoparticle delivers immunomodulatory compounds that reprogram macrophage function, converting tumor-promoting cells into anti-tumor cells without requiring complete repopulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional immunopotentiators are used, then some immune response enhancement occurs, but they cannot effectively re-polarize macrophages and improve tumor microenvironment

Engineering Contradiction:
Improveimmune response enhancementVSAvoidmacrophage polarization capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent designs a multi-functional nanoparticle system that simultaneously performs multiple functions: enhancing general immune response, specifically polarizing macrophages from M2 to M1, and improving overall tumor microenvironment. This universal approach replaces the need for multiple separate treatments with a single versatile platform.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent applies local quality modification by targeting specific molecular pathways and cell types within the tumor microenvironment. The nanoparticle is designed with specific surface properties and cargo composition that selectively interact with macrophages and their polarization pathways, providing localized and precise immunomodulation rather than broad unspecific effects.

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

The ginseng-derived nanoparticles effectively induce proliferation and activation of monocyte-macrophages, up-regulate immunologically active molecules, and re-polarize M2 type macrophages to M1 type, improving the tumor microenvironment and enhancing anti-tumor responses, with potential applications in treating various immune-related diseases and tumors.

Implementation Method 1

The preparation method of the ginseng-derived nanoparticles comprises the following steps: (1) squeezing fresh and washed ginseng by a low-speed screw extrusion technology to obtain a slurry, wherein the rotation speed of the low-speed screw extrusion is 30 to 60 rpm; (2) filtering the slurry obtained in step (1) through a sieve to remove impurities and collecting a filtrate; (3) sequentially subjecting the filtrate obtained in step (2) to low-speed, medium-speed, high-speed and ultra-speed centrifugation, discarding a precipitate after each centrifugation, and collecting a supernatant for the next centrifugation

Methodology Applied
Scientific EffectCentrifugation: Centrifugal Separation

Data Source

PatentEP3563861B1Ginseng-derived nanoparticle and preparation and application thereof
Publication Date: 2023.06.07 JIANGSU PROVINCE INST OF TRADITIONAL CHINESE MEDICINE
  • EP3563861B1 patent drawingFigure 1~2-3
  • EP3563861B1 patent drawingFigure 3~4
  • EP3563861B1 patent drawingFigure 5

AI summary

The invention discloses a ginseng-derived nanoparticle and a preparation method and application thereof. The ginseng-derived nanoparticle disclosed in the invention has a membrane structure, a particle size ranging from 150 to 500 nm and a peak particle size of 280 to 350 nm; and the ginseng-derived nanoparticle is prepared by multiple centrifugation, filtration and impurity removal. The ginseng-derived nanoparticle has good application prospects in developing drugs for preparing natural immunopotentiators and for preparing natural anti-tumor drugs.