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 the chemotherapy drug Taxol for the targeted therapy of head and neck cancer. Our research group has shown that over 50% of cancer tissues from head and neck cancer patients express a high level of folate receptor, raising exciting possibilities for the development of novel folate receptor-targeted therapeutics for this patient population. Our 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. In this project, we will further develop and characterize this ternary nanoparticle therapeutic drug. 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-nanoparticle (Hep-FA-Taxol) to a phase Ib clinical trial. Combined, these studies will 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 cancer. 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 reducing systemic toxicity
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