Project 4: Biodegradable Nanoparticle Formulated Taxol for Targeted Therapy of Head and Neck Cancer

Project Co-Leader: Shuming Nie, PhD Project Co-Leader: Lily Yang, MD, PhD Project Co-Leader: Nabil Saba, MD Co-Investigators: -Dirck Dillehay, DVM,PhD -Paraskevi Gannakakou, PhD -Selwyn J. Hurwitz, PhD -Rebecca Pentz, PhD -Dong M. Shin, MD

Nanosized Dendrimer Click for more detail

The use of nanoparticles for tumor targeting and drug delivery is one of the most exciting and clinically auspicious areas in nanotechnology. The proposed research aims to develop a new class of self-assembled and biodegradable nanoparticles carrying a chemotherapy drug Taxol for targeted therapy of the Head and Neck cancer. Our research team has recently developed a “ternary” nanoparticle structure by linking both a hydrophobic cancer drug (Taxol TM) and a tumor-targeting ligand [folic acid (FA)] to a hydrophilic and biodegradable polymer [heparin (Hep)], resulting in a tumor-targeted Taxol delivery nanoparticle (Hep-FA-Taxol). We demonstrate 17-fold higher tumor growth inhibition compared to free Taxol in a head and neck tumor xenograft model after systemic delivery of Hep-FA-Taxol nanocomplexes. Results of our research group have shown that over 20% of cancer tissues from head and cancer patients express a high level of folate receptor. These results have raised exciting possibilities for developing novel folate receptor- targeted therapeutic nanoparticle for therapy of head and neck cancer. In this project, we will further develop and characterize this “ternary” nanoparticle therapeutic drug (Hep-FA-Taxol). We plan to conduct preclinical studies to determine the specificity and efficacy of the Hep-FA-Taxol nanoparticle in Head and Neck tumor xenograft models. We will then determine biodistribution, toxicology, pharmacokinetic (PK), and pharmacodynamic (PD) in animals. The ultimate goal of this study is to bring this promising tumor targeted Taxol-nanoparticles (Hep-FA-Taxol) to a phase Ib clinical trial. Toward this goal, we propose to test the hypotheses that delivery of Taxol using Hep-FA-Taxol nanoparticles will improve (1) specific distribution of Taxol in tumor lesions expressing a high level of folate receptors, (2) intracellular concentration of Taxol to overcome drug resistance, and (3) therapeutic efficacy for the treatment of Head and Neck cancers.

The proposed research will allow us to conduct preclinical and clinical studies to bring this novel nanotherapeutic drug from bench top to clinical application. The development of this tumor targeted Taxol delivery nanoparticle may provide Head and Neck cancer patients with an effective treatment while reduce systemic toxicity.

Tumor Targeting by Endocytosis Click for more detail

Nanomedicines in Cancer Treatment Click for more detail

Folate receptor in Cancer Tissue Click for more detail