靶向巨噬细胞来调节肿瘤微环境是治疗癌症的一种有前景的策略。本研究利用硒纳米颗粒（SeNPs）和黄伞多糖成分（PAP-1a）开发了一种稳定的纳米药物（PAP-SeNPs），并报告了其物理稳定性、M2样巨噬细胞靶向功效和抗肝癌免疫治疗潜力。作为它们的分子机制。此外，还成功合成了零价且分散良好的球形PAP-SeNPs，平均尺寸为55.84nm，负电位为-51.45mV。此外，观察到制备的 PAP-SeNPs 在 4°C 下稳定 28 天。活体成像强调 PAP-SeNP 具有靶向所需免疫器官和肿瘤的双重作用。体外分析表明，PAP-SeNPs 将 M2 样巨噬细胞极化为 M1 表型，从而诱导肝癌细胞死亡，这是由巨噬细胞中时间依赖性溶酶体内吞作用触发的。从机制上讲，PAP-SeNPs显着激活Tlr4/Myd88/NF-κB轴，将促癌巨噬细胞转化为抑癌巨噬细胞，并成功启动抗肿瘤免疫治疗。此外，PAP-SeNPs还增强了CD3 CD4 T细胞和CD3 CD8 T细胞，从而进一步刺激抗肝癌免疫反应。这些结果表明，开发的 PAP-SeNP 是一种有前途的免疫刺激剂，可以辅助肝癌治疗。版权所有 © 2024。由 Elsevier B.V. 出版。

Targeting macrophages to regulate the tumor microenvironment is a promising strategy for treating cancer. This study developed a stable nano drug (PAP-SeNPs) using Se nanoparticles (SeNPs) and the Pholiota adiposa polysaccharide component (PAP-1a) and reported their physical stability, M2-like macrophages targeting efficacy and anti-hepatoma immunotherapy potential, as well as their molecular mechanisms. Furthermore, the zero-valent and well-dispersed spherical PAP-SeNPs were also successfully synthesized with an average size of 55.84 nm and a negative ζ-potential of -51.45 mV. Moreover, it was observed that the prepared PAP-SeNPs were stable for 28 days at 4 °C. Intravital imaging highlighted that PAP-SeNPs had the dual effect of targeting desirable immune organs and tumors. In vitro analyses showed that the PAP-SeNPs polarized M2-like macrophages towards the M1 phenotype to induce hepatoma cell death, triggered by the time-dependent lysosomal endocytosis in macrophages. Mechanistically, PAP-SeNPs significantly activated the Tlr4/Myd88/NF-κB axis to transform tumor-promoting macrophages into tumor-inhibiting macrophages and successfully initiated antitumor immunotherapy. Furthermore, PAP-SeNPs also enhanced CD3+CD4+ T cells and CD3+CD8+ T cells, thereby further stimulating anti-hepatoma immune responses. These results suggest that the developed PAP-SeNPs is a promising immunostimulant that can assist hepatoma therapy.Copyright © 2024. Published by Elsevier B.V.