单核吞噬细胞（MP）是宿主针对癌症的免疫防御的重要组成部分。然而，肿瘤浸润MP通常通过实体瘤中过度脂质积累触发的代谢转换而呈现耐受性和促肿瘤表型。受病毒感染介导的 MP 调节的启发，这里的包膜免疫代谢纳米颗粒 (immeNPs) 旨在共同传递病毒 RNA 类似物和脂肪酸氧化调节剂，以协同重塑瘤内 MP。这些immeNPs用癌细胞膜进行伪装以实现肿瘤归巢，并用抗CD163抗体进行调理以实现特异性MP识别和摄取。研究发现，内化的 immeNPs 协调脂质代谢重编程与先天免疫刺激，诱导 M2 至 M1 巨噬细胞复极化以及细胞毒性 T 细胞浸润的耐受性至免疫原性树突细胞分化。作者进一步证明，使用 immeNP 可以使免疫检查点阻断耐药的乳腺和卵巢肿瘤对抗 PD-1 疗法敏感，从而为扩大传统免疫疗法的潜力提供了一种有前途的策略。© 2023 作者。 《先进科学》由 Wiley-VCH GmbH 出版。

Mononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor-infiltrating MPs often present tolerogenic and pro-tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection-mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co-deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti-CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2-to-M1 macrophage repolarization and tolerogenic-to-immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti-PD-1 therapy in immune checkpoint blockade-resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.