ArticleInternational journal of nanomedicine2026
Foslip-Mediated Photodynamic Treatment Reprograms Macrophages Phenotype in Tri-Culture Head and Neck Cancer Spheroids.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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5 authors.
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Abstract
Background: The tumor microenvironment (TME) composition is among the critical events leading to the poor prognosis of head and neck cancers. TME includes immune cells, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAF), and other non-cancerous cells, which contribute to therapeutic outcome. The heterogeneity of the TME offers a multitude of potential targets for photodynamic therapy (PDT). Advanced 3D models that closely mimic the microenvironment are a promising tool to study tumor-stroma interactions, TAM plasticity and their impact on Foslip Objective: The aim of this study was to assess the effect of Foslip-PDT on photo-induced macrophage re-education in 3D tri-culture model composed of cancer cells, CAFs, and macrophages. Methods: A 3D model was established using FaDu cancer cells, MeWo fibroblasts, and PMA-differentiated U937 macrophages. The spheroids were characterized using immunochemistry, immunofluorescence, and qPCR. Foslip-based photoirradiation was applied to spheroids at different fluences to evaluate the photoinduced cell death. Macrophage phenotypes were assessed by flow cytometry. Results: The 3D tri-culture model displayed hallmarks of stromal-tumor interactions, including CAF clustering, macrophage infiltration (~30-40%), and epithelial-mesenchymal transition. Macrophages in the spheroids had prevailing M2 phenotype as deduced from overexpression of immunosuppressive markers (CD163, PDL-1, IL-10). The liposomal photosensitizer Foslip accumulated 2 to 3 times more in macrophage-enriched spheroids, however, PDT induced similar levels of cell death in all tested models. At the same time, Foslip-PDT produced immunomodulatory effect in tri-culture model characterized by the increase of CD80-M1 marker expression and the decrease in the expression of the CD206-M2 marker. Conclusion: The 3D tri-culture model integrated essential features of the HNSCC microenvironment. Foslip-PDT was effective in reprograming M2 macrophages to tumor-killing M1 macrophages. This study opens the way to combine direct tumor damage with TME modulation.
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