The use of nanoparticles for tumor targeting and drug delivery is one of the most exciting and clinicallyauspicious areas in nanotechnology. The proposed research aims to develop a new class of self-assembledand biodegradable nanoparticles carrying the chemotherapy drug Taxol for the targeted therapy of head andneck cancer. Our research group has shown that over 50% of cancer tissues from head and neck cancerpatients express a high level of folate receptor, raising exciting possibilities for the development of novelfolate 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-targetedTaxol delivery nanoparticle (Hep-FA-Taxol). We demonstrate 17-fold higher tumor growth inhibitioncompared to free Taxol in a head and neck tumor xenograft model after systemic delivery of Hep-FA-Taxolnanocomplexes. In this project, we will further develop and characterize this ternary nanoparticle therapeuticdrug. We plan to conduct preclinical studies to determine the specificity and efficacy of the Hep-FA-Taxolnanoparticle 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 thispromising tumor targeted Taxol-nanoparticle (Hep-FA-Taxol) to a phase Ib clinical trial. Combined, thesestudies 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) intracellularconcentration of Taxol to overcome drug resistance, and (3) therapeutic efficacy for the treatment of headand neck cancer. The proposed research will allow us to conduct preclinical and clinical studies to bring thisnovel nanotherapeutic drug from bench top to clinical application. The development of this tumor targetedTaxol delivery nanoparticle may provide head and neck cancer patients with an effective treatment whilereducing systemic toxicity
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