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Updated: May 31, 2026
Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma
Brent B Ward1, Thomas Dunham, Istvan J Majoros
1Michigan 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
Purpose:
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.
Materials And 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.
Insights
Folate-targeted chemotherapy using nanoparticles shows promise for treating head and neck squamous cell carcinoma (HNSCC). This targeted approach demonstrated efficacy and reduced toxicity in preclinical models, highlighting its potential in cancer treatment.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Nanoparticle drug delivery presents a promising strategy for cancer treatment.
- Head and neck squamous cell carcinoma (HNSCC) remains a significant clinical challenge.
- Folate binding protein-alpha (FBP-α) is a receptor implicated in HNSCC progression.
Purpose of the Study:
- To evaluate the efficacy and toxicity of folate-targeted chemotherapy in an HNSCC model.
- To determine the necessity of FBP-α receptor expression for targeted drug delivery.
- To assess the potential of nanoparticle-based chemotherapy in HNSCC treatment.
Main Methods:
- Screening of HNSCC cell lines (UM-SCC and ATCC) for FBP-α expression via quantitative real-time PCR.
- Fabrication of acetylated generation 5 dendrimers conjugated with folic acid and methotrexate.
- Administration of targeted therapy, free methotrexate, or saline to SCID mice bearing HNSCC tumors.
Main Results:
- Targeted therapy efficacy correlated with FBP-α receptor expression levels.
- Higher molar doses of targeted therapy were achievable compared to free drug.
- Treatment of high FBP-α expressing tumors showed increased efficacy and reduced systemic toxicity versus controls.
Conclusions:
- Dendrimer-based chemotherapy represents a novel therapeutic strategy for HNSCC.
- This approach demonstrates significant antitumor activity in HNSCC cell lines.
- The study underscores the potential of targeted nanoparticle delivery for HNSCC treatment.
