ArticleJournal of biomedical materials research. Part A2015
Conjugation of palmitic acid improves potency and longevity of siRNA delivered via endosomolytic polymer nanoparticles.
Article in Journal of biomedical materials research. Part A, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 30 citations in OpenAlex.
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Advancing Therapeutic Strategies with Polymeric Drug Conjugates for Nucleic Acid Delivery and Treatment.International journal of nanomedicine · 2025Review
- Recent advances in targeted delivery of non-coding RNA-based therapeutics for atherosclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract.International journal of molecular sciences · 2022Review
- Approaches to Modulate the Chronic Wound Environment Using Localized Nucleic Acid Delivery.Advances in wound care · 2021Review
- Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs.Acta biomaterialia · 2021Article
- Effect of Hydrophobicity on the Anticancer Activity of Fatty-Acyl-Conjugated CM4 in Breast Cancer Cells.ACS omega · 2020Article
- Amphiphilic Peptides for Efficient siRNA Delivery.Polymers · 2019Article
- Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability.ACS nano · 2019Article
- RNA interference-based therapy and its delivery systems.Cancer metastasis reviews · 2018Review
- Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Lipid-Drug Conjugate for Enhancing Drug Delivery.Molecular pharmaceutics · 2017Review
- Engineered Hydrogels for Local and Sustained Delivery of RNA-Interference Therapies.Advanced healthcare materials · 2017Review
- Local Delivery of PHD2 siRNA from ROS-Degradable Scaffolds to Promote Diabetic Wound Healing.Advanced healthcare materials · 2016Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Clinical translation of siRNA therapeutics has been limited by the inability to effectively overcome the rigorous delivery barriers associated with intracellular-acting biologics. Here, to address both potency and longevity of siRNA gene silencing, pH-responsive micellar nanoparticle (NP) carriers loaded with siRNA conjugated to palmitic acid (siRNA-PA) were investigated as a combined approach to improve siRNA endosomal escape and stability. Conjugation to hydrophobic PA improved NP loading efficiency relative to unmodified siRNA, enabling complete packaging of siRNA-PA at a lower polymer:siRNA ratio. PA conjugation also increased intracellular uptake of the nucleic acid cargo by 35-fold and produced a 3.1-fold increase in intracellular half-life. The higher uptake and improved retention of siRNA-PA NPs correlated to a 2- and 11-fold decrease in gene silencing IC50 in comparison to siRNA NPs in fibroblasts and mesenchymal stem cells, respectively, for both the model gene luciferase and the therapeutically relevant gene prolyl hydroxylase domain protein 2 (PHD2) . PA conjugation also significantly increased longevity of silencing activity following a single treatment in fibroblasts. Thus, conjugation of PA to siRNA paired with endosomolytic NPs is a promising approach to enhance the functional efficacy of siRNA in tissue regenerative and other applications.
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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.