Mesenchymal Stem Cells as a Delivery Platform for Photoactivable Nanoparticles for Cancer Therapy

Osteosarcoma patients are treated with the combination of multi-agent chemotherapy and surgery. With this treatment the 5-year event free survival of non-metastatic OS patients is 70% and between 20-25% of the OS patients with metastasis. This could be explained in part because chemotherapy is not selective for tumor cells, in part because micrometastasis are difficult to detect. In order to improve patient's survival rate, innovative treatments that specifically find and target osteosarcoma cells should be developed. The aim of this PhD thesis is test an innovative strategy to be used as neodajuvant therapy for osteosarcoma patients that do not respond to current standard therapy. The strategy takes advantage of the tumor-homing properties of mesenchymal stem cells to deliver selectively photoactivable nanoparticles to induce osteosarcoma cell death. In the first chapter of the thesis the efficacy of the strategy is demonstrated in vitro in bi-dimensional cultures. In the second chapter it is demonstrated that nanoparticles can be activated in the near infrared region of the visible spectrum, which can penetrate into deep tissues, and that FNP photoactivation results in tumor growth reduction in an animal model.