肿瘤相关巨噬细胞（TAMs）的M1极化是突破免疫抑制性肿瘤微环境（TME）治疗障碍的一种有希望的方法。然而，作为临床应用于化疗后的癌症患者的免疫增强剂，茯苓多糖（PPS）的免疫调节机制和潜力尚不清楚。在这里，我们介绍了蔗糖胺修饰的PPS载荷超顺磁性纳米复合材料（Man/PPS-SPIONs），用于协同促进TAMs的M1极化和随之而来的联合抗乳腺癌治疗。一旦被M2样TAMs内化，Man/PPS-SPIONs中释放的PPS通过IFN-γ的分泌和下游NF-κB通路的激活诱导M1极化。纳米复合材料中的超顺磁性纳米颗粒介导Fenton反应，产生OH·并激活后续的NF-κB/MAPK通路，进一步促进M1极化。因此，Man/PPS-SPIONs通过“IFN-γ-Fenton-NF-κB/MAPK”多途径建立了M1极化的正反馈循环，在TME中引发一系列抗肿瘤免疫反应，并在联合抗癌治疗中具有潜在前景。我们的研究提供了一种利用组合天然碳水化合物聚合物和铁基材料扩大TME工程的新策略。版权所有 © 2023 Elsevier B.V. 发布。

M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.Copyright © 2023. Published by Elsevier B.V.