Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles

Area of Science:

• Oncology
• Nanomedicine
• Immunology

Background:

• Proton pump inhibitors can enhance cancer therapies by reducing tumor acidity and boosting anti-tumor immunity.
• Intracellular pH regulation is crucial for melanoma progression and immune suppression by myeloid cells.

Purpose of the Study:

• To develop poly(l-lactide-co-glycolide) nanoparticles loaded with esomeprazole (ESO-NPs) for intracellular pH regulation in melanoma and myeloid-derived suppressor cells (MDSCs).
• To investigate the effects of ESO-NPs on melanoma cell characteristics and immune checkpoint expression.
• To evaluate the impact of ESO-NPs on immunosuppressive molecules in patient-derived and in vitro-induced MDSCs.

Main Methods:

• Development of esomeprazole-loaded poly(l-lactide-co-glycolide) nanoparticles (ESO-NPs).
• Treatment of melanoma cells and myeloid-derived suppressor cells (MDSCs) with ESO-NPs.
• Analysis of intracellular pH, melanin content, and expression of key proteins (MITF, PVR, PD-L1, CD206, CD163, CD86, HLA-DR) using flow cytometry and other relevant assays.

Main Results:

• ESO-NPs induced alkalinization and reduced melanin content in melanoma cells, decreasing MITF, PVR, and PD-L1 expression.
• Treatment of patient-derived MDSCs with ESO-NPs reduced PD-L1, CD206, and CD163 expression.
• ESO-NPs induced CD86 and HLA-DR expression in in vitro-induced MDSCs.

Conclusions:

• Reprogramming intracellular pH of melanoma and immunosuppressive myeloid cells with ESO-NPs modulates proteins involved in cancer therapy resistance and immunosuppression.
• ESO-NPs show potential for improving patient response to cancer immunotherapies.