Gold Nanoparticle CpG Conjugates for Lymphoma Therapy

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Solution Overview

Problem

Current treatments for diffuse large B cell lymphoma (DLBCL) have limited effectiveness, with only 33% overall survival rate for high-risk patients, and existing immunotherapies like checkpoint inhibition and CAR-T therapy are not sufficient for all patients, necessitating innovative approaches for improved outcomes.

Innovation Solution

Development of immune conjugate nanoparticles that combine CpG motifs with gold nanoparticles for targeted immunotherapy and photothermal therapy, enhancing immune stimulation and apoptosis in lymphoma cells by delivering CpG motifs directly to lymphoid organs and tumor sites, using class B and C CpG oligodeoxynucleotides with spacers for improved stability and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard chemo-immunotherapy is used for DLBCL treatment, then treatment can be administered with existing protocols, but treatment effectiveness is limited with only 33% overall survival rate for high-risk patients

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidresponse rate variability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines gold nanoparticles with CpG oligodeoxynucleotides to create composite immune conjugate nanoparticles. This composite structure integrates the targeting and delivery capabilities of nanoparticles with the immunostimulatory properties of CpG, achieving enhanced therapeutic effectiveness (60-70% survival rate) while maintaining adaptability to different patient responses through selective activation of immune pathways.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent merges immunotherapy (CpG stimulation) with photothermal therapy (gold nanoparticle light absorption) into a single conjugate system. This combination allows simultaneous immune activation and direct tumor cell killing through photothermal effects, improving overall treatment effectiveness while providing versatile mechanisms to address variable patient responses.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If higher doses of CpG are administered to improve immune stimulation, then therapeutic effect increases, but toxicity increases

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The gold nanoparticle acts as an intermediary carrier that delivers CpG oligodeoxynucleotides to target cells. This mediator enables effective immune stimulation at lower CpG doses by enhancing cellular uptake and retention, thereby reducing toxicity while maintaining therapeutic effect. The nanoparticle protects CpG from degradation and facilitates targeted delivery to lymphoid organs and tumor sites.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical state and delivery parameters of CpG by conjugating it to gold nanoparticles. This transformation allows CpG to be delivered in a controlled manner with optimized dosage, achieving enhanced therapeutic effects at lower concentrations and reduced toxicity compared to free CpG administration.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If free CpG is administered systemically, then immune stimulation occurs, but distribution to lymphoid organs and tumor sites is insufficient

Engineering Contradiction:
Improveimmune stimulationVSAvoidtargeted delivery efficiency
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The gold nanoparticle serves as an intermediary delivery vehicle that transports CpG oligodeoxynucleotides to target sites. This mediator exploits the enhanced permeability and retention effect in tumors and the natural affinity of nanoparticles for lymphoid organs, achieving efficient targeted delivery and enhanced immune stimulation at the desired locations.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent segments the delivery system by using nanoparticles to carry CpG to specific anatomical regions (lymphoid organs and tumor sites) rather than relying on uniform systemic distribution. This segmentation enables localized accumulation and enhanced effectiveness at target sites while reducing off-target effects.

Inventive Principle:
Principle #1Segmentation

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 nanoparticles significantly reduce lymphoma cell viability, induce apoptosis, and increase cytokine and marker expression, demonstrating enhanced therapeutic effects compared to free CpGs, with potential for improved survival rates and reduced toxicity at lower CpG dosing.

Implementation Method 1

photothermal therapy

Methodology Applied
Scientific EffectPhotothermal conversion: Absorption (EM radiation)

Implementation Method 2

gold nanoparticles... for photothermal therapy

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 3

CpG motifs with gold nanoparticles for targeted immunotherapy... delivering CpG motifs directly to lymphoid organs and tumor sites

Methodology Applied
Scientific EffectToll-like receptor recognition:

Data Source

PatentUS20220401576A1Gold nanoparticles/nanoshells immune conjugates for enhanced immunotherapy and photothermal therapy for hematologic malignancies
Publication Date: 2022.12.22 NORTHWESTERN UNIV
  • US20220401576A1 patent drawing
  • US20220401576A1 patent drawing
  • US20220401576A1 patent drawing

AI summary

Disclosed herein are CpG conjugated nanoparticles for immunotherapy and photothermal therapy. The composition comprises class B CpG conjugated nanoparticles and/or a class C CpG conjugated nanoparticles where the class B CpG conjugated nanoparticles comprises a nanoparticle core and a class B CpG conjugated thereto and the class C CpG conjugated nanoparticles comprises a nanoparticle core and a class C CpG conjugated thereto.