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ZnPPIX-Loaded Nanoemulsions Reprogram Immunosuppressive Macrophages in Vitro: A Potential Strategy for Glioblastoma
Ada Tushe1, Elena Marinelli2, Sara Zumerle1
1Immunology and Molecular Oncology Unit, Veneto Institute of Oncology (IOV)-IRCCS, Padua, Italy.
International Journal of Nanomedicine
|October 13, 2025
Summary
Nanomedicine targets immunosuppressive cells in glioblastoma (GBM). A novel nanoemulsion (NE-ZnPPIX) inhibits heme-oxygenase-1 (HO-1), reprogramming macrophages to reduce tumor-promoting activity and enhance immunotherapy efficacy.
Area of Science:
- Neuro-oncology
- Nanomedicine
- Immunotherapy
Background:
- Glioblastoma (GBM) has poor prognosis despite aggressive treatment.
- The tumor microenvironment (TME) in GBM is immunosuppressive, hindering immunotherapy.
- Bone marrow-derived macrophages (BMDMs) drive immunosuppression in GBM.
- Heme-oxygenase-1 (HO-1) inhibition shows potential for reprogramming BMDMs.
Purpose of the Study:
- To develop a nanomedicine approach targeting immunosuppressive cells in GBM.
- To investigate the efficacy of a nanoemulsion loaded with a HO-1 inhibitor (NE-ZnPPIX).
- To assess the immunomodulatory effects of NE-ZnPPIX on macrophages within the GBM TME.
Main Methods:
- Developed an oil-in-water nanoemulsion (NE-ZnPPIX) using microfluidics.
- Utilized the intrinsic fluorescence of zinc protoporphyrin IX (ZnPPIX) for cellular uptake tracking.
- Performed functional assays to evaluate immunomodulatory effects on macrophages.
Main Results:
- NE-ZnPPIX selectively targets immunosuppressive myeloid cells, GBM cells, and monocytes.
- Encapsulated ZnPPIX effectively reduces immunosuppressive activity of macrophages.
- NE-ZnPPIX decreases CD163 expression, a marker of pro-tumoral immunosuppressive phenotype.
Conclusions:
- NE-ZnPPIX is a promising strategy for remodeling the GBM TME.
- This approach can enhance immunotherapy by overcoming tumor immune evasion.
- NE-ZnPPIX offers a novel therapeutic avenue for glioblastoma treatment.
