title: Leukocytes as carriers for targeted cancer drug delivery.
abstract: BACKGROUND
  Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites.
  
  
  METHODS
  This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process.
  
  
  CONCLUSIONS
  Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues.
authors.affiliation: Cornell University, Department of Biomedical Engineering , Ithaca, NY 14853 , USA mike.king@cornell.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mitchell
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D004337:Drug Carriers / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D037742:Nanotubes, Carbon / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008670:Metals; D037742:Nanotubes, Carbon; D011108:Polymers
keywords: cancer; leukocyte; metastasis; nanomedicine