Article

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: 1.28). 06/2011; 69(9):2452-9. DOI: 10.1016/j.joms.2010.12.041
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: István J Majoros, Aug 12, 2015
2 Followers
 · 
164 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanotechnology, a separate field of knowledge since 1980s, involves utilization of nanomaterials not only in electronics and catalysis, but also in biomedical research including drug delivery, bioimaging, biomedical-diagnostics and tissue engineering. Multidisciplinary of this science has led to the development of different areas of technology and might contribute to innovations that will, as a final consequence, help humanity. Dendrimers are large and complex molecules that are characterized by well-defined nanoscale architecture, monodispersity and structural versatility. These highly interesting polymers consist of three elements: core, branches and peripheral groups. There is a wide variety of potential applications of dendritic polymers. One of the most promising is utilization of polyamidoamine (PAMAM) dendrimers as drug delivery devices. Among pharmaceuticals that have been connected with different types of dendrimers are nonsteroidal anti-inflammatory drugs (NSAIDs), anticancer drugs and other. Dendrimers application as drug carriers improves pharmacokinetic properties of drug particles, decreases drugs' side effects and, by possibility of surface modification with different ligands, enables to target specific tissues and tumor cells. Dendrimers might be also utilized as devices for delivery of genetic material and contrast agents for magnetic resonance imaging (MRI).
    Nano brief reports and reviews 05/2012; 06(06). DOI:10.1142/S1793292011002871 · 1.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Development of carrier systems to improve oral bioavailability and target drugs to specific sites continues to be an unmet need. The goal of this study was to evaluate the potential of anionic generation (G) 6.5 poly(amido amine) (PAMAM) dendrimers in oral drug delivery by assessing their in vivo oral translocation. G6.5-COOH dendrimers were characterized for their physiochemical characteristics and acute oral toxicity was assessed in CD-1 mice. The dendrimers were labeled with 125I and their stability evaluated. Oral bioavailability was assessed in the same mouse model. Investigation of the radioactivity profile in plasma, revealed presence of both large and small molecular weight compounds. Detailed area under the curve analysis suggests an effective 9.4% bioavailability of radiolabeled marker associated with G6.5-COOH. Results reported here suggest the potential of dendrimers in permeating gastrointestinal barriers in vivo.
    Molecular Pharmaceutics 01/2013; 10(3). DOI:10.1021/mp300436c · 4.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The desire to target therapies to specific cancers while leaving the host unharmed remains an ongoing quest for scientists, surgeons, radiation oncologists, and medical oncologists. In recent years, great scientific progress has been made in targeted therapies. Although many modalities remain in preclinical validation, some advances affect patient care today. This article summarizes the concepts of targeting and explores current examples of successful targeting and emerging targeting technologies in head and neck oncology.
    Oral and maxillofacial surgery clinics of North America 02/2013; 25(1):83–92. DOI:10.1016/j.coms.2012.11.006 · 0.48 Impact Factor
Show more