Polyporus umbellatus polysaccharide iron-based nanocomposite for synergistic M1 polarization of TAMs and combinational anti-breast cancer therapy

• Published in: International journal of biological macromolecules Vol. 251; p. 126323
• Main Authors: Liu, Tingting, Han, Tao, Liu, Congyan, Ge, Chang, Jiang, Xi, Liu, Yuping, Kong, Fei, Su, Xiangyu, Shi, Jiachen, Su, Wenting, Li, Xiaoqi, Chen, Yan, Zhang, Huangqin, Ma, Qiuling, Qu, Ding
• Format: Journal Article
• Language: English
• Published: Netherlands 01.11.2023
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cell Line, Tumor; Female; Fungal Polysaccharides - chemistry; Fungal Polysaccharides - pharmacology; Humans; Interferon-gamma - metabolism; Iron - chemistry; Mice; Nanocomposites - chemistry; NF-kappa B - metabolism; Polyporus - chemistry; Polysaccharides - chemistry; Polysaccharides - pharmacology; RAW 264.7 Cells; Tumor Microenvironment - drug effects; Tumor-Associated Macrophages - drug effects; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; Polyporus umbellatus polysaccharide; Breast cancer; Iron-based nanocomposites; M1 polarization; Tumor-associated macrophages
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.126323

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.