NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

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ABSTRACT The excitement about nanomedicine stems from the potential application of nanoscience to solve challenging medical problems. Coupled with the fenestrated bone marrow environment (BME) and the highly specific metal- binding matrix of the bone, cancer-killing nanoparticles (NPs) are uniquely suited to overcome current impediments to achieving durable therapy for bone lesions. A variety of NPs used to deliver drugs to the BME and has successfully demonstrated efficacy. However, nanoparticles are also effective as therapeutic agents, yet this feature is underutilized in the treatment of bone lesions. Recently, we developed radionuclide stimulated therapy that leverages the interaction of Cerenkov radiation emitting radionuclides to stimulate the production of reactive oxygen species from photosensitizers. The combination of these drugs will allow the treatment of diverse diseases without the limitation of tissue depth that affects light-based therapies. In this proposal, we will apply this concept to disrupt the protective interaction of cancer cells with stromal cells. The inactivation of both cell types will enhance treatment response. Accordingly, we will utilize 1. inorganic nanoparticles to inactive the protective stromal cells, and 2. nanoliposomes to deliver high payloads to the BME. The studies will be conducted with in vivo and in vitro models of cancer. Imaging will be used to monitor treatment response. At the completion of this study, we would develop new nanoplatforms for the treatment and imaging of cancer and bone lesions.