Novel polyurethane-based ionene nanoparticles electrostatically stabilized with hyaluronic acid for effective gene therapy

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. [Display omitted] •Novel gene delivery system based on cationic polyurethane ionene (CPUI) nanoparticles, for breast cancer treatment.•A complex utilizing electrostatic interaction between CPUI nanoparticles and siRNA.•For active targeting, hyaluronic acid (HA) was used for coating of the complexes.•Cellular uptake, cytotoxicity, and suppression of the STAT3 gene were enhanced for the targeted nanocarriers.•Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in vivo.