Polysialic-emodin self-assembled nanoparticles synergize with PD-1 inhibitors to enhance tumor immunotherapy

In this study, emodin (ED) and polysialic acid (PSA) were synthesized into a compound called PSA-ED. The PSA-ED self-assembled into nanoparticles (PE-NS) using a nano-precipitation method. According to the results of particle size analyzer, the particle size of PE-NS was 180.7 ± 1.60 nm, the polydispersity index (PDI) was 0.263 ± 0.090, and the ζ potential was -17.1 ± 0.9 mV. In vitro cellular experiments confirmed that compared to free emodin, PE-NS exhibited significantly higher cellular uptake in RAW264.7 cells. In addition, in vivo imaging demonstrated enhanced fluorescence accumulation in tumors. This indicated that PE-NS possesses the ability to effectively target tumor-associated macrophages (TAMs). We conducted experiments using a mouse model of the B16F10 tumor, treating the mice with PD-1 antibody, PE-NS, and various doses of PE-NS + anti-PD-1 antibody, and compared them with untreated controls. In the PE-NS and anti-PD-1 antibody combination therapy group, there was a notable decrease in the proportion of M2-TAMs and CD4 + Fop3+ T cells, alongside a significant increase in the proportion of M1-TAMs and CD8+ T cells, resulting in an increased tumor inhibition rate. The combination of PE-NS and anti-PD-1 antibody exhibited synergistic antitumor activity, enhancing the effectiveness of PD-1 checkpoint blockers in the mouse melanoma models. In conclusion, the combination of PE-NS and anti-PD-1 antibody immunotherapy holds great promise in improving the therapeutic effects of melanoma treatment and may offer a novel strategy for clinical application.