title: Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies.
abstract: BACKGROUND
  Despite therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges. The helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is expected to become available in the near future.
  
  
  METHODS
  The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL, Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts.
  
  
  RESULTS
  One hundred twenty nine papers were included in the review. These papers defined hurdles in RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also briefly reviewed chemical modification.
  
  
  CONCLUSIONS
  Delivery of siRNA to the target site is the biggest challenge for its application in the clinic. The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity. In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for medical application of RNAi-based therapeutics is needed.
authors.forename: Neda
authors.initials: N
authors.lastname: Shajari
authors.forename: Behzad
authors.initials: B
authors.lastname: Mansoori
authors.forename: Sadaf
authors.initials: S
authors.lastname: Davudian
authors.forename: Ali
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering
keywords: Cancer; RNAi; chemical modification; lipid-based nanoparticle; polymeric nanoparticle; systemic delivery