ArticleBiomaterials advances2022
Hyaluronate-coated perfluoroalkyl polyamine prodrugs as bioactive siRNA delivery systems for the treatment of peritoneal cancers.
Article in Biomaterials advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Nanoparticles Bounded to Interfering RNAs as a Therapy for Pancreatic Cancer: A Systematic Review.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyPooled it
- Tumor Lipidomic Changes after Treatment with Polymeric Hydroxychloroquine in a Syngeneic Murine Model of Pancreatic Cancer.ACS omega · 2026Article
- Polyamine metabolism and anti-tumor immunity.Frontiers in immunology · 2025Review
- Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction.International journal of molecular sciences · 2024Article
- Polymer-Based Drug Delivery Systems for Cancer Therapeutics.Polymers · 2024Review
- Core polymer optimization of ternary siRNA nanoparticles enhances in vivo safety, pharmacokinetics, and tumor gene silencing.Biomaterials · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
RNA interference (RNAi) is an emerging therapeutic modality for cancer, which remains in critical need of effective delivery vectors due to the unfavorable biopharmaceutical properties of small RNAs. Polyamines are essential for functioning of mammalian cells. Dysregulated polyamine metabolism is found in many cancers and has been an attractive therapeutic target in combination therapies. Combination therapies based on drugs that affect polyamine metabolism and nucleic acids promise to enhance anticancer activity due to a cooperative effect on multiple oncogenic pathways. Here, we report bioactive polycationic prodrug (F-PaP) based on an anticancer polyamine analog bisethylnorspermine (BENSpm) modified with perfluoroalkyl moieties. Following encapsulation of siRNA, F-PaP/siRNA nanoparticles were coated with hyaluronic acid (HA) to form ternary nanoparticles HA@F-PaP/siRNA. The presence of perfluoroalkyl moieties and HA reduced cell membrane toxicity and improved stability of the particles with cooperatively enhanced siRNA delivery in pancreatic and colon cancer cell lines. We then tested a therapeutic hypothesis that combining BENSpm with siRNA silencing of polo-like kinase 1 (PLK1) would result in cooperative cancer cell killing. HA@F-PaP/siPLK1 induced polyamine catabolism and cell cycle arrest, leading to enhanced apoptosis in the tested cell lines. The HA-coated nanoparticles facilitated tumor accumulation and contributed to strong tumor inhibition and favorable modulation of the immune tumor microenvironment in orthotopic pancreatic cancer model. Combination anticancer therapy with polyamine prodrug-mediated delivery of siRNA. Hyaluronate coating of the siRNA nanoparticles facilitates selective accumulation in orthotopic pancreatic tumors. Perfluoroalkyl conjugation reduces toxicity and improves gene silencing effect. Nanoparticle treatment induces polyamine catabolism and cell cycle arrest leading to strong tumor inhibition and favorable modulation of immune tumor microenvironment.
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