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Novel Polyurethane-Based Ionene Nanoparticles Electrostatically Stabilized With Hyaluronic Acid for Effective Gene Therapy Publisher Pubmed



Mahdieh A1 ; Motasadizadeh H2 ; Maghsoudian S3 ; Sabzevari A4, 5 ; Khalili F3 ; Yeganeh H6 ; Nystrom B7
Authors
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Authors Affiliations
  1. 1. Department of Pharmacy, Section for Pharmaceutics and Social Pharmacy, University of Oslo, Oslo, Norway
  2. 2. Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Polymer Faculty, Biomedical Engineering Department, Meybod University, Meybod, Yazd, Iran
  5. 5. Polymer Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran
  6. 6. Iran Polymer and Petrochemical Institute, Tehran, Iran
  7. 7. Department of Chemistry, University of Oslo, Oslo, Norway

Source: Colloids and Surfaces B: Biointerfaces Published:2024


Abstract

Gene therapy is considered to be a valuable strategy for effective cancer treatment. However, the development of effective delivery systems that can specifically deliver gene materials, such as siRNA to tumor tissues plays a critical role in cancer therapy. In the present study, we have developed a novel complex that is based on an electrostatic interaction between cationic polyurethane ionene (CPUI) nanoparticles and an anti-signal transducer and activator of transcription 3 (STAT3) siRNA. For active targeting, hyaluronic acid (HA) was used to coat the complexes, which significantly reduced the cytotoxicity of the blank nanocarriers while demonstrating high transport efficiency of the siRNA via the CD44-mediated endocytosis pathway in MCF-7 breast cancer cells. The targeted nanocarriers (HA/CPUI/siRNA) showed significantly higher cellular internalization in flow cytometry and confocal microscopy compared with the non-targeted system (CPUI/siRNA). In addition, the incorporation of HA on the surface of the complexes resulted in significantly greater suppression of the STAT3 gene compared to the corresponding non-targeted formulation. Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in 4T1 breast tumor-bearing mice. Therefore, HA/CPUI/siRNA nanocarriers are an interesting option for the siRNA-targeted treatment of breast cancer cells. © 2024 The Authors