pHLIP Peptides Target Acidity in Activated Macrophages.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Immunology

Background:

• Acidity is a potential biomarker for targeting metabolically active cells in diseased tissues.
• pH low insertion peptides (pHLIPs) are established for targeting cell-surface acidity.

Purpose of the Study:

• To investigate the targeting of activated macrophages using pH low insertion peptides (pHLIPs).
• To evaluate pHLIPs as a potential biomarker for diseased tissues.

Main Methods:

• Studies were conducted in cell cultures and mouse models of lung inflammation and tumors.
• Techniques included fluorescence microscopy, whole-body and organ imaging, immunohistochemistry, and FACS analysis.

Main Results:

• Activated macrophages readily internalized fluorescent pHLIPs, with higher uptake in glycolytic macrophages.
• Fluorescent pHLIPs successfully targeted LPS-induced lung inflammation and tumor-associated macrophages in mice.
• pHLIPs targeted specific macrophage populations (CD45+, CD11b+, F4/80+, CD206+) within tumors and lymph nodes.

Conclusions:

• pHLIP peptides insert into cell membranes at low pH, and are internalized by macrophages via endosomes.
• Targeting activated macrophages with pHLIPs presents opportunities for clinical visualization and therapeutic interventions in diseased tissues.