title: Progress and perspective of inorganic nanoparticle-based siRNA delivery systems.
abstract: BACKGROUND
  Small interfering RNA (siRNA) is an effective method for regulating the expression of proteins, even "undruggable" ones that are nearly impossible to target through traditional small molecule therapeutics. Delivery to the cell and then to the cytosol is the primary requirement for realization of therapeutic potential of siRNA.
  
  
  METHODS
  We summarize recent advances in the design of inorganic nanoparticle with surface functionality and physicochemical properties engineered for siRNA delivery. Specifically, we discuss the main approaches developed so far to load siRNA into/onto NPs, and NP surface chemistry engineered for enhanced intracellular siRNA delivery, endosomal escape, and targeted delivery of siRNA to disease cells and tissues.
  
  
  CONCLUSIONS
  Several challenges remain in developing inorganic NPs for efficient and effective siRNA delivery. Getting the material to the chosen site is important, however the greatest hurdle may well be delivery into the cytosol, either through efficient endosomal escape or by direct cytosolic siRNA delivery. Effective delivery at the organismic and cellular level coupled with biocompatible vehicles with low immunogenic response will facilitate the clinical translation of RNAi for the treatment of genetic diseases.
authors.affiliation: a Department of Chemistry , University of Massachusetts-Amherst , Amherst , MA , USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a Department of Chemistry , University of Massachusetts-Amherst , Amherst , MA , USA.|b Chinese Academy of Sciences (CAS) Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for Nanoscience and Technology , Beijing , China.
authors.forename: Shuaidong
authors.initials: S
authors.lastname: Huo
authors.affiliation: a Department of Chemistry , University of Massachusetts-Amherst , Amherst , MA , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hardie
authors.affiliation: b Chinese Academy of Sciences (CAS) Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for Nanoscience and Technology , Beijing , China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: a Department of Chemistry , University of Massachusetts-Amherst , Amherst , MA , USA.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Rotello
mesh_terms: D003600:Cytosol / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D013499:Surface Properties
chemical_list: D034741:RNA, Small Interfering
keywords: Cancer therapy; RNAi; inorganic nanoparticle; siRNA delivery; surface chemistry