{ "abstract": "As a prevalent malignancy, liver cancer ranks as the third most common cause of cancer mortality globally. Within the tumor microenvironment, tumor-associated macrophages (TAMs) exhibit contrasting functional phenotypes: the anti-tumor M1 type and the pro-tumor M2 type. Reprogramming TAMs from the M2 to the M1 phenotype has emerged as a promising immunotherapeutic strategy. Here, we engineered a multi-nano therapeutic system, PAH@HMMDN@R848, by loading a TLR7/8 agonist (R848) onto hollow MnO2 nanoparticles (HMMDN) and coating with polyallylamine hydrochloride (PAH). In vitro, this system efficiently repolarized M2 macrophages to the M1 phenotype, evidenced by decreased CD206, Arg-1, IL-10 and increased CD80, iNOS, TNF-α (P < 0.05). Under acidic/glutathione-rich conditions, HMMDN degraded to release Mn2+, which served as a T1-weighted MRI contrast agent with a high relaxivity (r1 = 5.255 mM-1 s -1). Mechanistically, PAH@HMMDN@R848 activated both NF-κB (via R848) and STING (via Mn2+) pathways, leading to synergistic M1 polarization. In a subcutaneous H22 liver cancer mouse model, intratumoral injection of PAH@HMMDN@R848 significantly suppressed tumor growth (tumor inhibition rate 80.6%) without obvious systemic toxicity. Immunohistochemistry and cytokine analysis revealed that the treatment increased M1 macrophage infiltration (CD80+) and reduced M2 macrophages (CD206+) within tumors, along with elevated TNF-α/iNOS and decreased IL-10/Arg-1. This study presents a multifunctional nanoplatform capable of TAMs reprogramming and MRI diagnosis, offering a promising approach for liver cancer theranostics.", "abstract_shown": true, "affiliations": [ "Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China", "Innovation Centre for Science and Technology of North Sichuan Medical College, Nanchong, Sichuan, China", "Biotechnology Innovation Drug Application and Transformation Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan Province, China", "Department of Ultrasound, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0 ], "name": "Pei-pei He" }, { "affs": [ 1 ], "name": "Zheng-ju Hou" }, { "affs": [ 2 ], "name": "Han-mei Li" }, { "affs": [ 3 ], "name": "Ji-xuan Zhang" }, { "name": "An-Qi Chen" }, { "name": "Quan-you Miao" }, { "name": "Chao-Feng Yang" }, { "name": "Jin-hong Yu" }, { "name": "Yang Li" } ], "bibtex": "https://research.draconitic.com/paper/feqcrh1craywt.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0358567", "fulltext_url": null, "id": "feqcrh1craywt", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0358567", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2403|Immune cells in cancer" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Engineering and technology/Nanotechnology/Nanoparticles" ], [ "plos", "/Medicine and health sciences/Diagnostic medicine/Diagnostic radiology/Magnetic resonance imaging" ], [ "plos", "/Medicine and health sciences/Gastroenterology and hepatology/Liver diseases/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Oncology/Cancer treatment" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Carcinoma/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Malignant tumors" ], [ "plos", "/Medicine and health sciences/Radiology and imaging/Diagnostic radiology/Magnetic resonance imaging" ], [ "plos", "/Research and analysis methods/Imaging techniques/Diagnostic radiology/Magnetic resonance imaging" ] ], "openalex": "W7213561385", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358567&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-18", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/feqcrh1craywt.ris", "sources": [ { "first_seen": "2026-10-30T12:17:49Z", "native_id": "10.1371/journal.pone.0358567", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0358567" } ], "subjects": [ { "field": "medicine", "origin": "plos:diagnostic radiology", "subfield": "imaging" }, { "field": "medicine", "origin": "plos:oncology", "subfield": "oncology" } ], "title": "Reprogramming M2 macrophages via TLR7/8 agonist-loaded hollow MnO₂ nanovehicles to suppress the progression of liver cancer", "title_text": "Reprogramming M2 macrophages via TLR7/8 agonist-loaded hollow MnO₂ nanovehicles to suppress the progression of liver cancer", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:49Z", "url": "https://research.draconitic.com/paper/feqcrh1craywt", "venue": "PLOS One", "versions": [] }