ArticleProceedings of the National Academy of Sciences of the United States of America2017
Protein nanocages that penetrate airway mucus and tumor tissue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Encapsulation of Protein-Based Drug Carriers for Controlled Loading and Releasing Efficiency: A Review.The protein journal · 2026Review
- Ferritin-Based Nanomotors for Deep Glioblastoma Penetration and Enhanced Drug Delivery.Macromolecular bioscience · 2026Article
- Granzyme B-mimetic nanozyme for nanovesicle targeted anticancer applications.Nature communications · 2026Article
- From Pharmacological Uncertainty to Inhalation Development: An Evidence-Gated Roadmap forDrug design, development and therapy · 2026Review
- Molecular Mechanisms and Biomedical Applications of Ferritin Nanocages: A Comprehensive Review of Self-Assembly, Engineering, and Multifunctional Delivery Platforms.International journal of nanomedicine · 2026Review
- Simulation of drug transport in airway surface liquid considering mucus flow and ciliary interaction.Scientific reports · 2025Article
- Design and application of ferritin-based nanomedicine for targeted cancer therapy.Nanomedicine (London, England) · 2025Review
- Assembly of Genetically Engineered Ionizable Protein Nanocage-based Nanozymes for Intracellular Superoxide Scavenging.Nature communications · 2025Article
- Breath and Beyond: Advances in Nanomedicine for Oral and Intranasal Aerosol Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Nanomedicines for Pulmonary Drug Delivery: Overcoming Barriers in the Treatment of Respiratory Infections and Lung Cancer.Pharmaceutics · 2024Review
- Self-Assembly of Heterogeneous Ferritin Nanocages for Tumor Uptake and Penetration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate.Cell death & disease · 2024Article
- Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice.Nature communications · 2024Article
- Enteral Route Nanomedicine for Cancer Therapy.International journal of nanomedicine · 2024Review
- Recombinant ferritins for multimodal nanomedicine.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Computational fluid dynamics modeling of aerosol particle transport through lung airway mucosa.Computers & chemical engineering · 2023Article
- Article
- Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel.Acta pharmaceutica Sinica. B · 2023Article
- Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier.Journal of nanobiotechnology · 2023Article
- Article
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Authors and funding
8 authors.
Funding
Abstract
Reports on drug delivery systems capable of overcoming multiple biological barriers are rare. We introduce a nanoparticle-based drug delivery technology capable of rapidly penetrating both lung tumor tissue and the mucus layer that protects airway tissues from nanoscale objects. Specifically, human ferritin heavy-chain nanocages (FTn) were functionalized with polyethylene glycol (PEG) in a unique manner that allows robust control over PEG location (nanoparticle surface only) and surface density. We varied PEG surface density and molecular weight to discover PEGylated FTn that rapidly penetrated both mucus barriers and tumor tissues in vitro and in vivo. Upon inhalation in mice, PEGylated FTn with optimized PEGylation rapidly penetrated the mucus gel layer and thus provided a uniform distribution throughout the airways. Subsequently, PEGylated FTn preferentially penetrated and distributed within orthotopic lung tumor tissue, and selectively entered cancer cells, in a transferrin receptor 1-dependent manner, which is up-regulated in most cancers. To test the potential therapeutic benefits, doxorubicin (DOX) was conjugated to PEGylated FTn via an acid-labile linker to facilitate intracellular release of DOX after cell entry. Inhalation of DOX-loaded PEGylated FTn led to 60% survival, compared with 10% survival in the group that inhaled DOX in solution at the maximally tolerated dose, in a murine model of malignant airway lung cancer. This approach may provide benefits as an adjuvant therapy combined with systemic chemo- or immunotherapy or as a stand-alone therapy for patients with tumors confined to the airways.
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Registered trials
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