Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Int J Biol Macromol. 2023 Nov 1;251:126323. doi: 10.1016/j.ijbiomac.2023.126323. Epub 2023 Aug 14.
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.
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）治疗障碍的一种很有前途的方法。然而，多糖作为癌症患者化疗后的免疫增强剂，其免疫调节机制和潜力尚不清楚。在这里，我们提出了甘露糖修饰的负载多糖的超顺磁性铁基纳米复合材料（Man/PPS-SPIONs），用于协同 M1 极化 TAMs 并进行联合抗乳腺癌治疗。一旦被 M2 样 TAMs 内化，Man/PPS-SPIONs 中释放的 PPS 通过 IFN-γ 分泌和下游 NF-κB 途径激活诱导 M1 极化。纳米复合材料中的 SPIONs 介导芬顿反应，产生 OH·并激活随后的 NF-κB/MAPK 途径，进一步促进 M1 极化。Man/PPS-SPIONs 因此建立了由“IFN-γ-Fenton-NF-κB/MAPK”多途径驱动的 M1 极化的正反馈回路，导致 TME 中的一系列抗肿瘤免疫反应，并在联合抗癌治疗中具有很大的潜力。我们的研究提供了一种通过组合天然碳水化合物聚合物和铁基材料来增强 TME 工程的新策略。
