title: Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Nanoparticle drug delivery offers a potential solution in the treatment of cancer. Using a heterotopic tumor model for head and neck squamous cell carcinoma (HNSCC), tumors of variable folate binding protein-alpha (FBP-α) have been treated to delineate receptor necessity as well as efficacy and toxicity of folate targeted chemotherapy.
  
  
  METHODS
  University of Michigan Squamous Cell Carcinoma (UM-SCC) and American Type Culture Collection (ATCC) cell lines were screened using quantitative real-time polymerase chain reaction for FBP-α expression. Acetylated generation 5 dendrimers conjugated to the targeting moiety folic acid and the therapeutic moiety methotrexate were fabricated and administered to severe combined immunodeficiency (SCID) CB-17 mice inoculated with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer cells. Mice were injected with targeted therapy, free methotrexate, or saline control and monitored for drug efficacy and toxicity.
  
  
  RESULTS
  Targeted therapy was effective relative to receptor level expression. Targeted therapy could be delivered in molar doses 3 times that of free drug. The treatment of a high folate expression tumor cell population was noted to have increased efficacy over saline (P < .01) and free methotrexate (P = .03) as well as decreased systemic toxicity.
  
  
  CONCLUSIONS
  This report represents the first translation of dendrimer-based chemotherapy to HNSCC and underscores its effectiveness as an antitumor agent in human cancer cell lines with lower levels of FBP-α than the in vitro and in vivo models previously reported.
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, and Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI 48109, USA. bward@umich.edu
authors.forename: Brent B
authors.initials: BB
authors.lastname: Ward
authors.forename: Thomas
authors.initials: T
authors.lastname: Dunham
authors.forename: Istvan J
authors.initials: IJ
authors.lastname: Majoros
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D050091:Dendrimers; D004195:Disease Models, Animal; D005260:Female; D058975:Folate Receptor 1 / Q000096:biosynthesis; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods*; D009368:Neoplasm Transplantation
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D058975:Folate Receptor 1; C104700:PAMAM Starburst; D008727:Methotrexate