Folate Receptor β (FRβ) Expression on Myeloid Cells and the Impact of Reticuloendothelial System on...

Area of Science:

• Immunology
• Nanotechnology
• Oncology

Background:

• Folate receptor beta (FRβ) mediates folate uptake in myeloid immune cells, crucial for tumor microenvironment infiltration.
• Folate-functionalized nanoparticles face clearance limitations by the reticuloendothelial system (RES).
• Understanding FRβ expression in myeloid cells is vital for optimizing folate-targeted drug delivery.

Purpose of the Study:

• Quantify FRβ-expressing myeloid cell subtypes in tumors at various cancer stages.
• Compare FRβ+ myeloid cell distribution in organs of tumor-bearing versus healthy animals.
• Evaluate the association between FRβ+ cell density and the tumor-targeting efficacy of folate-functionalized nanoparticles.

Main Methods:

• Utilized a mouse breast cancer model.
• Analyzed FRβ expression and myeloid cell infiltration in tumors and various organs.
• Assessed the biodistribution and tumor-targeting efficacy of folate-functionalized cyclodextrin nanoparticles.

Main Results:

• Myeloid cell infiltration and FRβ expression increased during tumorigenesis.
• CD206+ macrophages showed high FRβ expression in both healthy and tumor-bearing mice.
• Tumor-bearing mice exhibited increased myeloid cells, particularly granulocytes, across multiple organs.
• FRβ+ immune cell density in tumors did not correlate with nanoparticle targeting efficacy.
• Lungs showed preferential nanoparticle accumulation, with FRβ+CD206+ macrophages actively engulfing nanoparticles.

Conclusions:

• Tumorigenesis alters FR levels and myeloid cell distribution across organs, influencing nanoparticle delivery.
• FRβ+CD206+ macrophages in the lungs are key players in folate-functionalized nanoparticle uptake.
• These findings necessitate consideration of systemic immune cell changes for effective nanoparticle-based drug delivery.