Interaction of M2 macrophages with hepatocellular carcinoma co-culture system in the presence of doxorubicin-loaded nanoparticles

Tumor-associated macrophages (TAMs) play a crucial role in the proliferation and metastasis of cancer cells in solid tumors. TAMs-cancer cell co-culture models provide the opportunity to study the impact of TAMs on the efficiency of therapeutic agents in combination with drug delivery systems. In this study, we aimed to investigate the impact of M0 and M2 phenotypes of TAMs on the cytotoxicity of doxorubicin-loaded poly (n-butyl cyanoacrylate) nanoparticles on hepatocellular carcinoma cells using a co-culture model. In this study, THP-1 cells were polarized into M0 and M2 phenotypes and co-cultured with the cancer cells. The results indicated that M2 cells represented a higher expression of CD14, CD16, CD80, and CD86 markers compared to M0 cells. Moreover, NPs demonstrated higher cytotoxicity in the co-culture model compared to the conventional 2D culture model. Besides, the proliferation of the cancer cells significantly declined following treatment with the serum-free supernatant of the NPs-treated M2 cells after incubation of 48 h, while the supernatant of untreated cells promoted the proliferation of the cancer cells. In addition, the intracellular cytokines levels of TAMs did not significantly change following treatment by the NPs. In conclusion, TAMs play a determinant role in the cytotoxicity aspect of the NPs for hepatocellular carcinoma cells.