title: Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.
abstract: BACKGROUND
  Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment.
  
  
  METHODS
  In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA).
  
  
  CONCLUSIONS
  Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.
authors.affiliation: a Institute of Technology , University of Tartu , Tartu , Estonia.
authors.forename: Kaido
authors.initials: K
authors.lastname: Kurrikoff
authors.affiliation: b Department of Neurochemistry , Stockholm Universitet , Stockholm , Sweden.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gestin
authors.affiliation: a Institute of Technology , University of Tartu , Tartu , Estonia.|b Department of Neurochemistry , Stockholm Universitet , Stockholm , Sweden.
authors.forename: Ülo
authors.initials: Ü
authors.lastname: Langel
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage*; D053758:Nanoparticles; D009696:Nucleic Acids / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000008:administration & dosage
chemical_list: D057846:Cell-Penetrating Peptides; D046911:Macromolecular Substances; D009696:Nucleic Acids; D034741:RNA, Small Interfering
keywords: Activatable CPP; CPP; cell penetrating peptides; drug delivery vectors; in vivo delivery vectors; peptide vectors