Targeted Dendrimer Chemotherapy in an Animal Model for Head and Neck Squamous Cell Carcinoma

Michigan Nanotechnology Institute for Medicine and Biological Sciences, and Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons (Impact Factor: 1.43). 06/2011; 69(9):2452-9. DOI: 10.1016/j.joms.2010.12.041
Source: PubMed


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.
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.
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.
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.

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Available from: István J Majoros,
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    • "Chemotherapeutic drugs (eg, paclitaxel, doxorubicin) conjugated with FA have been shown not only to be selectively transported into KB cells,14,15 Bel 7402 cells,16 and nude mice xenograft tumors, but also to achieve better antitumor results. Saba et al detected the FR in 45% of primary squamous cell carcinomas of the head and neck and 40% of corresponding lymph node metastases.13 Ward et al made acetylated generation 5 dendrimers conjugated with FA and methotrexate as the therapeutic moiety in compound reagents and administered them to nude mice with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer xenografts.17 They found this targeted therapy could be delivered in molar doses three times that of the free drug and with lower systemic toxicity. "
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