ArticleNature communications2025
Modulating tumor collagen fiber alignment for enhanced lung cancer immunotherapy via inhaled RNA.
Article in Nature communications, 2025. 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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The trial behind it
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
14 citing papers in PubMed.
- Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system.International journal of pharmaceutics: X · 2026Review
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Collagen-Binding IL-15 Immunocytokine Armed Oncolytic Adenovirus Establishes a Self-Reinforcing Immunostimulatory Milieu to Potentiate Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Supermeres Containing the Discoidin Domain Receptor 1 Extracellular Domain Promote Collagen Alignment and Immune Exclusion in Microsatellite-Stable Colorectal Cancer.Cancer research communications · 2026Article
- Nanomaterial Strategies for Pulmonary Delivery of Immunotherapeutics in Lung Cancer Treatment.Advanced healthcare materials · 2026Review
- Recent Advances in Lipid Nanoparticle-Mediated Respiratory and Gastrointestinal Mucosal Delivery of Nucleic Acids.Bioengineering (Basel, Switzerland) · 2026Review
- Target-Product and Translational Design Principles for Inhalable RNA Nanomedicines.Pharmaceutics · 2026Review
- Unlocking the potential of mRNA nanomedicines for comprehensive fibrosis therapy.Molecular therapy. Nucleic acids · 2026Review
- Tumor microenvironment and mechanotransduction pathways: Novel targets and new directions for cancer therapy.Mechanobiology in medicine · 2026Review
- Mechanical regulation of microenvironment remodeling in brain tumors: from mechanism to therapy.Journal of neuroinflammation · 2026Review
- Additive anti-tumor and immunomodulatory effects of Sporoderm-removed Ganoderma lucidum spore powder and anti-PD-L1 antibody in lung cancer mice.Discover oncology · 2026Article
- Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.Journal of biomedical science · 2026Review
- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- Reconstructing the Tumor Mechanical Microenvironment in Organoids: From Mechanical Cues to Biomimetic Modeling and Therapeutic Insights.International journal of medical sciences · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical effectiveness of immunotherapies for lung cancers has been greatly hindered by the immune-excluded and immunosuppressive tumor microenvironment (TME) and limited pulmonary accessibility of therapeutics. Here, we develop an inhalable lipid nanoparticle (LNP) system that enables simultaneous delivery of mRNA encoding anti-discoidin domain receptor 1 (DDR1) single-chain variable fragments (mscFv) and siRNA targeting PD-L1 (siPD-L1) into pulmonary cancer cells. The secreted anti-DDR1 scFv blocks the binding of DDR1 extracellular domain to collagen, disrupting collagen fiber alignment and reducing tumor stiffness, thereby facilitating T cell infiltration. Meanwhile, PD-L1 silencing alleviates immunosuppression and preserves T cell cytotoxicity. In vivo results demonstrate that mscFv@LNP induces collagen fiber rearrangement and diminishes tumor stiffness. In both orthotopic and metastatic mouse models of lung cancer, inhalation of mscFv/siPD-L1@LNP promotes tumor regression and extends overall survival. This strategy could be broadly applicable to solid tumors and benefit other cancer immunotherapies by addressing the universally hostile TME involved in tumor progression.
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Registered trials
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.