[Angelica sinensis polysaccharide-chitosan nanosystem synergizes with radiotherapy to enhance anti-tumor immunity and suppress tumor growth].

To enhance the immunomodulatory effect of Angelica sinensis polysaccharide(ASP) on the tumor microenvironment, this study prepared ASP-chitosan nanoparticles(ASP-NPs) using a molecular self-assembly technique. The preparation process was optimized through single-factor investigation. The results from dynamic light scattering and transmission electron microscopy showed that ASP-NPs had a particle size of(313.1±23.3) nm, with uniform distribution and regular morphology. In the 4T1 breast cancer mouse model, ASP-NPs combined with radiotherapy(RT) significantly inhibited tumor growth through two administration routes(intratumoral injection and intravenous injection): the tumor inhibition rate reached 69% in the intratumoral injection group and 47% in the intravenous injection group, both significantly higher than that of the RT group(P<0.05). Serum cytokine assays showed that interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α) were significantly elevated under both administration methods(P<0.05). Tumor hematoxylin-eosin(HE) staining revealed that the combined treatment group had significantly expanded necrotic areas in tumor tissues and obvious inflammatory cell infiltration. Immunohistochemical and TUNEL assays showed that ASP-NPs could inhibit tumor cell proliferation and promote apoptosis. Flow cytometry further compared and analyzed dendritic cells(DCs) in tumor-draining lymph nodes and effector T cell subsets in tumor tissues, showing that both intratumoral and intravenous injections increased mature DCs in lymph nodes by over 11.2%. The infiltration rates of CD4~+ T cells and CD8~+ T cells in tumor tissues were significantly increased by 1.6-fold and 2.5-fold respectively compared with the simple RT group(P<0.05). In conclusion, this study reveals the immune activation effect of ASP-NPs combined with radiotherapy, achieving better anti-tumor efficacy, and providing important experimental evidence for tumor immune combination therapy strategies based on traditional Chinese medicine polysaccharides.