Grant: Project Grant

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most frequent cancer. Surgery, external beam radiotherapy, and chemotherapy are used to treat SCCHN, which have many side effects including damage to healthy tissue, nausea, loss of hair, loss of appetite and weight, and overall, negatively affect quality of life. Thus, more precise therapies with better efficacy, fewer side effects, and improved functional outcomes are needed. To achieve this, we must drastically re-think how we deliver treatments such as radioactive ions and chemotherapeutic drugs to tumors. Antibodies and peptides have advanced the development of precision therapies as they bind specifically to cancer cells. However, effectiveness of these therapies have been underwhelming. Antibodies can be improved by attaching radioactive ions and/or chemotherapy drugs for enhanced potency. Despite some clinical successes, the development of these antibody-based radionuclide therapy and nuclear imaging drugs is challenging, as it requires stable attachment of radioactive ions to the sensitive antibody structure and they have long blood circulation times. As one solution, we propose a biocompatible cancer drug delivery system. These nanoparticles (nanovesicles) are tiny tumor delivery vehicles ~150 nm wide which can be loaded with many combinations of different radionuclides and drugs. These tumor delivery vehicles are called mimetic nanovesicles (M-NVs) and are made from recycled cell membranes. We can attach cancer-targeting antibodies and radionuclides to the surface of these M-NVs and load the inside with chemotherapy drugs to provide selective tumor delivery. We envision our M-NV technology as a natural engineering platform to combine the tumor targeting properties of antibodies, the cancer-killing power of chemotherapy drugs and radionuclides, and the diagnostic power of nuclear imaging. Unlike most nanoparticles, these biologically distribute very quickly and are non-toxic carries.