• Development of hyaluronic acid-based nanocarriers for delivery of siRNAs in breast cancer therapy
  • Fereshteh Rahdan,1 Zeinab Chaharlashkar,2 Effat Alizadeh,3,*
    1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
    2. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
    3. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.


  • Introduction: Gene therapy based on RNA interference has been considered as a useful therapeutic strategy for the treatment of breast cancer. However, small interfering RNA (siRNA) delivery has several limitations, including off-target effects, unwanted tissue accumulation, unsuccessful intracellular delivery, high toxicity, and instability in the bloodstream, according to clinical trial reports. Therefore, the development of safe and efficient vectors required for optimal siRNA delivery. Hyaluronic acid (HA) is a linear negatively-charged mucopolysaccharide which has the advantage of being biocompatible, non-cytotoxic, and biodegradable. Due to its carboxylic and hydroxyl groups, it is suitable for desired chemical modifications to create safe and high-performance carriers for delivering siRNAs. This review discusses the prospects, recent advances, and future challenges of HA-mediated delivery of siRNAs in breast cancer therapy.
  • Methods: Original articles published since 2005 on HA-based nanocarriers in the field of siRNA delivery for breast cancer therapy were searched from Web of Science, Google Scholar, Elsevier, Scopus, and PubMed databases. Using these data, the properties, applications and challenges of HA-based nanocarriers were discussed.
  • Results: HA exists naturally in various parts of the human body, so the cellular adaptation is tolerable for the immune system. Furthermore, HA cannot load negatively charged siRNA due to its negative charge. Therefore, by making changes in the composition and functional groups of HA or by conjugating HA to positively charged polymers or cationic groups, new vectors with modified surface charge can be created to be complexed with siRNA. HA-based nanocomplexes have physicochemical properties that are selected for controlled release of siRNAs to cancer cells and increasing the lifetime of siRNA by providing enzymatic stability against degradation.
  • Conclusion: The results show that HA-based nanoparticles can be used as a suitable carrier for the optimal delivery of therapeutic siRNA to breast cancer cells.
  • Keywords: Hyaluronic Acid, nanocarriers, small interfering RNA, breast cancer therapy