Nanostructured Lipid Carriers as Effective Delivery Systems of Photosensitizers for Photodynamic Therapy against Gliobastoma Multiforme

Glioblastoma multiforme is the most malignant and invasive brain tumor, characterized by a heterogeneous histological nature. This primary tumor is considered a grade IV neoplasm with astrocytic differentiation; the average incidence rate is 3.2 cases per 100.000 people and the median age of diagnosis is 64 years with typically mean survival rates after diagnosis less than two years. Currently, standard therapies generally include surgical resection, combined with radiotherapy, chemotherapy, but these approaches minimally extend the average patient survival. In the last decades, biomedical research and, in particular, nanomedicine have developed several strategies in order to enhance conventional anticancer therapies. Nanocarriers represent an innovative and versatile solution, as they can be used both for imaging and therapeutic purposes. In this thesis, nanostructured lipidic carriers (NLCs), loaded with the photosensitizers chlorin e6 (Ce6) were developed and tested for their anticancer potential against glioblastoma multiforme with photodynamic therapy (PDT). Furthermore, the surface of NLCs is functionalized with the peptide Angiopep-2 (Ang) which interact with receptors overexpressed on brain endothelial cells and in glioblastoma cells, promoting preferentially internalization in tumor cells and fostering the crossing of the blood-brain barrier. In PDT, chlorin e6 is a chlorophyll derivative and, after irradiation at a specific wavelength (660 nm) is able to produce singlet oxygen and other reactive oxygen species that induce several death mechanism in cancer cells. This work aims at characterizing and testing the efficacy of NLCs and evaluate their photodynamic activity in vitro against a glioblastoma multiforme model. Nanocarriers represent innovative tools in order to improve the efficacy of traditional therapies and to reduce their related side effects.