Adhered Polymeric Particles for Macrophage Phenotype Retention

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Solution Overview

Problem

Adoptive macrophage therapy has faced challenges as macrophages quickly lose their desired phenotype, compromising therapeutic efficacy.

Innovation Solution

Polymeric particles with phagocytosis-resistant polarizing agents are attached to the cell surface of macrophages or monocytes, regulating and maintaining the desired M1 or M2 phenotype for sustained therapeutic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If macrophages are used in adoptive therapy, then therapeutic potential is achieved, but the macrophages quickly lose their desired phenotype

Engineering Contradiction:
Improvephenotype retentionVSAvoidtherapeutic efficacy duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by pre-attaching polymeric particles containing polarizing agents to the macrophage cell surface before therapy. These particles are anchored in advance to ensure the macrophages maintain their desired phenotype (M1 or M2) throughout the therapeutic process, preventing the phenotype loss that normally occurs during adoptive therapy

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses polymeric particles as an intermediary substance that mediates between the therapeutic goal and the macrophage cell. These particles carry polarizing agents that continuously regulate the macrophage phenotype, acting as a bridge to maintain cellular function without requiring genetic modification of the macrophages themselves

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If genetic modification is used to maintain macrophage phenotype, then phenotype stability is improved, but cell activity and mobility are compromised

Engineering Contradiction:
Improvephenotype stabilityVSAvoidcell mobility and activity
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent employs polymeric particles as an intermediary that provides phenotype stability without direct genetic modification. These particles attach to the cell surface and deliver polarizing agents, achieving stable phenotype maintenance while preserving the macrophage's natural mobility and biological activity, unlike genetic modification approaches

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical-chemical parameters of the macrophage environment by attaching polymeric particles with specific polarizing agents to the cell surface. This external parameter modification achieves phenotype stability without altering the internal genetic parameters of the cell, thereby maintaining cell functionality and mobility

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

The approach allows macrophages to retain their phenotype, enhancing therapeutic flexibility and efficacy by ensuring prolonged activity and mobility without genetic modification.

Implementation Method 1

These polymeric particles are phagocytosis-resistant and comprise polarizing agents which can regulate the cell's phenotype

Methodology Applied
Scientific EffectPhagocytosis resistance:

Implementation Method 2

attaching the polymeric particle to the cell surface causes the cell to assume the desired phenotype (e.g., M1 or M2, generally corresponding to pro-inflammatory and anti-inflammatory phenotypes)

Methodology Applied
Scientific EffectPolarization regulation:

Data Source

PatentUS12414999B2Compositions and methods relating to macrophages and/or monocytes with adhered particles
Publication Date: 2025.09.16 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US12414999B2 patent drawing
  • US12414999B2 patent drawing
  • US12414999B2 patent drawing

AI summary

Provided herein are polymeric particles and compositions (i.e., “backpacks”) that can adhere to cells and provide delivery of payload immunomodulatory agents to those cells. For examples, the particles can adhere to macrophages and/or monocytes and release cytokines that promote an M1 or M2 phenotype to improve therapeutic efficacy of the cells.