ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Nanoparticle-mediated gene silencing confers radioprotection to salivary glands in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 97 citations in OpenAlex.
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- Advances in Gene Therapy for Xerostomia: Current Perspectives and Future Directions: A Narrative Review.Health science reports · 2026Article
- Salivary gland tissue chip screening identifies candidate radioprotective drugs.Communications medicine · 2025Article
- Advancing Head and Neck Cancer Therapies: From Conventional Treatments to Emerging Strategies.Biomedicines · 2025Review
- Salivary Gland Bioengineering.Bioengineering (Basel, Switzerland) · 2023Review
- Effect of nanoparticle-mediated delivery of SFRP4 siRNA for treating Dupuytren disease.Gene therapy · 2023Article
- Metabolomics analysis of pathways underlying radiation-induced salivary gland dysfunction stages.PloS one · 2023Article
- Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023Article
- Platelet membrane-camouflaged nanoparticles carry microRNA inhibitor against myocardial ischaemia‒reperfusion injury.Journal of nanobiotechnology · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Insights into Nanomedicine for Head and Neck Cancer Diagnosis and Treatment.Materials (Basel, Switzerland) · 2022Review
- Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids.Frontiers in bioengineering and biotechnology · 2022Article
- Laminin-1 Peptides Conjugated to Fibrin Hydrogels Promote Salivary Gland Regeneration in Irradiated Mouse Submandibular Glands.Frontiers in bioengineering and biotechnology · 2021Article
- Pharmacological Activation of cGAS for Cancer Immunotherapy.Frontiers in immunology · 2021Article
- Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions.Journal of clinical medicine · 2020Review
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Building a Functional Salivary Gland for Cell-Based Therapy: More than Secretory Epithelial Acini.Tissue engineering. Part A · 2020Review
- Rigor and reproducibility in polymer nanoparticle synthesis and characterization.RSC advances · 2020Article
- Microparticle Depots for Controlled and Sustained Release of Endosomolytic Nanoparticles.Cellular and molecular bioengineering · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Radiation treatment of head and neck cancers causes irreversible damage of the salivary glands (SG). Here, we introduce a preclinical mouse model for small-interfering RNA (siRNA)-based gene silencing to provide protection of SG from radiation-induced apoptosis. Novel, pH-responsive nanoparticles complexed with siRNAs were introduced into mouse submandibular glands (SMG) by retroductal injection to modulate gene expression in vivo. To validate this approach, we first targeted Nkcc1, an ion transporter that is essential for saliva secretion. Nkcc1 siRNA delivery resulted in efficient knockdown, as quantified at the mRNA and the protein levels, and the functional result of Nkcc1 knockdown phenocopied the severe decrease in saliva secretion, characteristic of the systemic Nkcc1 gene knockout. To establish a strategy to prevent apoptotic cell loss due to radiation damage, siRNAs targeting the proapoptotic Pkcδ gene were administered into SMG before ionizing radiation. Knockdown of Pkcδ not only reduced the number of apoptotic cells during the acute phase of radiation damage, but also markedly improved saliva secretion at 3 months in irradiated animals, indicating that this treatment confers protection from hyposalivation. These results demonstrate that nanoparticle delivery of siRNAs targeting a proapoptotic gene is a localized, nonviral, and effective means of conferring radioprotection to the SGs.
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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.