免疫系统紊乱已被证实是各种癌症，包括前列腺癌（PCa）发展的主要因素。脂质纳米粒子（LNPs）已被证实能诱导肝细胞癌的抗肿瘤免疫反应。因此，我们评估了载有免疫基因调控因子的LNPs治疗PCa的潜力。通过使用GEO数据库中PCa的单细胞测序数据，我们确定了巨噬细胞和T细胞是PCa异质性的主要细胞类型。此外，JUN和ATF3，T细胞和巨噬细胞的主要基因，在PCa中显著低表达，预示着不良预后。装载JUN和ATF3 pDNA的LNPs减缓了肿瘤携带小鼠的转移命运，降低了肿瘤刺激因子的分泌，证明了加速巨噬细胞极化和增加T细胞浸润。这些发现表明，通过LNPs结合两者具有体内功效。 LNPs在体外显著促进了巨噬细胞活性，并抑制了PCa细胞的免疫逃避。总的来说，我们的工作确定了装载调控因子的LNPs显着促进了巨噬细胞极化和T细胞活性，并增强了免疫监视以抑制PCa的进展，深入了解了PCa免疫微环境的异质性，并有望利用LNPs实现PCa治疗的优化。 Copyright © 2023 Elsevier Ltd.发表。

Immune system perturbation has been revealed as a main contributor to the development of various types of cancer, including prostate cancer (PCa). Lipid nanoparticles (LNPs) have been revealed to induce anti-tumor immunity for hepatocellular carcinoma. Thus, we evaluated the potential of LNPs loaded with immune gene regulons for treating PCa. By using single-cell sequencing data of PCa in the GEO database, we identified that macrophages and T cells were the main cell types of PCa heterogeneity. Furthermore, JUN and ATF3, major genes in T cells and macrophages, were significantly poorly expressed in PCa, which predicted a poor prognosis. LNPs loaded with JUN and ATF3 pDNA slowed the metastatic fate in tumor-bearing mice and reduced secretion of tumor-stimulating factors, as evidenced by accelerated macrophage polarization and increased T-cell infiltration. These findings suggested that the combination of the two via LNPs had efficacy in vivo. LNPs significantly promoted macrophage activity and inhibited the immune evasion of PCa cells in vitro. Collectively, our work identified LNPs loaded with regulons significantly promoted macrophage polarization and T cell activity and enhanced immune surveillance to inhibit PCa progression, gaining insights into the heterogeneity of PCa immune microenvironment and holding promise for optimized PCa treatment using LNPs.Copyright © 2023. Published by Elsevier Ltd.