ArticleProceedings of the National Academy of Sciences of the United States of America2022
pH-degradable, bisphosphonate-loaded nanogels attenuate liver fibrosis by repolarization of M2-type macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 33 citations in OpenAlex.
- Antifibrotic hydrogel strategies for scarless tissue regeneration: mechanisms, design, and application.Bioactive materials · 2027Review
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- A multiscale pathoanatomical atlas guides the design of functionally graded, anatomically intelligent implants for chronic osteomyelitis.Bioactive materials · 2026Article
- An Injectable Metal-Drug Supramolecular Condensate Enables Radiosensitization and Systemic Antitumor Immunity for Post-Surgical Osteosarcoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting FGG alleviates cholestatic fibrosis by inhibiting hepatic stellate cell activation and regulating macrophage homeostasis.Journal of nanobiotechnology · 2026Article
- Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026Review
- Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.Journal of clinical medicine · 2025Review
- Injectable immunoregulatory hydrogels sequentially drive phenotypic polarization of macrophages for infected wound healing.Bioactive materials · 2024Article
- Advancements in Targeting Macrophage Senescence for Age-Associated Conditions.Aging and disease · 2024Review
- Commentary on: Safety and feasibility of percutaneous needle tunneling with platelet-rich plasma injections for Peyronie's disease in the outpatient setting: a pilot study.International journal of impotence research · 2024Article
- HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.Nature communications · 2023Article
- Macrophages and platelets in liver fibrosis and hepatocellular carcinoma.Frontiers in immunology · 2023Review
- The Role of Macrophages in Liver Fibrosis: New Therapeutic Opportunities.International journal of molecular sciences · 2022Review
- Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).Journal of clinical medicine · 2022Article
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Authors and funding
21 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Immune-suppressive (M2-type) macrophages can contribute to the progression of cancer and fibrosis. In chronic liver diseases, M2-type macrophages promote the replacement of functional parenchyma by collagen-rich scar tissue. Here, we aim to prevent liver fibrosis progression by repolarizing liver M2-type macrophages toward a nonfibrotic phenotype by applying a pH-degradable, squaric ester–based nanogel carrier system. This nanotechnology platform enables a selective conjugation of the highly water-soluble bisphosphonate alendronate, a macrophage-repolarizing agent that intrinsically targets bone tissue. The covalent delivery system, however, promotes the drug’s safe and efficient delivery to nonparenchymal cells of fibrotic livers after intravenous administration. The bisphosphonate payload does not eliminate but instead reprograms profibrotic M2- toward antifibrotic M1-type macrophages in vitro and potently prevents liver fibrosis progression in vivo, mainly via induction of a fibrolytic phenotype, as demonstrated by transcriptomic and proteomic analyses. Therefore, the alendronate-loaded squaric ester–based nanogels represent an attractive approach for nanotherapeutic interventions in fibrosis and other diseases driven by M2-type macrophages, including cancer.
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