ArticleActa pharmaceutica Sinica. B2022
Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment.
Article in Acta pharmaceutica Sinica. B, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting circulating tumor cell‒neutrophil interactions: nanoengineered strategies for inhibiting cancer metastasis.Journal of nanobiotechnology · 2025Review
- Neutrophil extracellular traps in cancer: From mechanisms to treatments.Clinical and translational medicine · 2025Review
- New structural scaffolds to enhance the metabolic stability of arginine-derived PAD4 inhibitors.Results in chemistry · 2025Article
- NETs - as predictors and targets of supportive therapy for cancer treatment.Frontiers in immunology · 2025Review
- PAD4 Inhibitor-Loaded Layered Double Hydroxide Nanosheets as a Multifunctional Nanoplatform for Photodynamic Therapy-Mediated Tumor Metastasis Treatment.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Imaging and Therapy of Tumors Based on Neutrophil Extracellular Traps.Small science · 2024Article
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- PAD4 Inhibitor-Functionalized Layered Double Hydroxide Nanosheets for Synergistic Sonodynamic Therapy/Immunotherapy Of Tumor Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Theranostic nanoparticles ZIF-8@ICG for pH/NIR-responsive drug-release and NIR-guided chemo-phototherapy against non-small-cell lung cancer.Journal of materials science. Materials in medicine · 2024Article
- Article
- Structure-Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy.Pharmaceutics · 2024Review
- Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation.International journal of nanomedicine · 2024Review
- Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.Acta pharmaceutica Sinica. B · 2023Article
- PAD4 and Its Inhibitors in Cancer Progression and Prognosis.Pharmaceutics · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.