title: Intracellular delivery of nanocarriers and targeting to subcellular organelles.
abstract: BACKGROUND
  Recent trends in drug delivery indicate a steady increase in the use of targeted therapeutics to enhance the specific delivery of biologically active payloads to diseased tissues while avoiding their off-target effects. However, in most cases, the distribution of therapeutics inside cells and their targeting to intracellular targets still presents a formidable challenge. The main barrier to intracellular delivery is the translocation of therapeutic molecules across the cell membrane, and ultimately through the membrane of their intracellular target organelles. Another prerequisite for an efficient intracellular localization of active molecules is their escape from the endocytic pathway.
  
  
  METHODS
  Pharmaceutical nanocarriers have demonstrated substantial advantages for the delivery of therapeutics and offer elegant platforms for intracellular delivery. They can be engineered with both intracellular and organelle-specific targeting moieties to deliver encapsulated or conjugated cargoes to specific sub-cellular targets. In this review, we discuss important aspects of intracellular drug targeting and delivery with a focus on nanocarriers modified with various ligands to specifically target intracellular organelles.
  
  
  CONCLUSIONS
  Intracellular delivery affords selective localization of molecules to their target site, thus maximizing their efficacy and safety. The advent of novel nanocarriers and targeting ligands as well as exploration of alternate routes for the intracellular delivery and targeting has prompted extensive research, and promises an exciting future for this field.
authors.affiliation: a 1 Northeastern University, Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences , Boston, MA 02115, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Jhaveri
authors.affiliation: b 2 Northeastern University, Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences , Boston, MA 02115, USA v.torchilin@neu.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Torchilin
mesh_terms: D001692:Biological Transport; D004337:Drug Carriers / Q000493:pharmacokinetics*; D006801:Humans; D008024:Ligands; D053758:Nanoparticles; D015388:Organelles / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D008024:Ligands
keywords: cell-penetrating peptides; cytoplasm; intracellular delivery; liposomes; macromolecules; mitochondria; nanocarriers; nuclei; polymeric micelles