Particle Shape Modulates the Function of Adoptive Macrophage Transfers

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• Adoptive cell transfers (ACTs) are emerging for nanoparticle delivery.
• Macrophages (Mφ) are promising carriers due to their targeting and phagocytic capabilities.
• Understanding how particle shape affects Mφ function in ACTs is crucial.

Purpose of the Study:

• To investigate macrophage interactions with spherical and discoidal particles.
• To evaluate the impact of particle shape on Mφ function and tumor delivery.
• To determine if particle shape can be a design parameter for ACTs.

Main Methods:

• Macrophage interaction studies with biodegradable spherical and discoidal particles.
• In vivo adoptive transfer of Mφ-S and Mφ-D to B16-F10 tumor models.
• Analysis of Mφ phenotype, transcriptional, chromatin accessibility, and protein state.

Main Results:

• Mφ-S and Mφ-D exhibited enhanced tumor targeting compared to free microparticles.
• Mφ-S showed epigenetic changes and biomarkers associated with a pro-inflammatory phenotype.
• Mφ-D displayed a mixed pro- and anti-inflammatory profile, indicating functional flexibility.

Conclusions:

• Particle shape significantly influences macrophage phenotype and function in ACTs.
• Biodegradable particle shape can be engineered to modulate Mφ behavior for improved therapeutic delivery.
• This study provides a design strategy for optimizing ACTs using particle shape.