Development and characterization of a 3D model of Oral Squamous Cell Carcinoma for application in photodynamic therapy using phenyl thio-phthalocyanine nanocapsules

Abstract

The tumor environment is highly complex which makes the development of new therapeutic approaches challenging. However, the vast majority of in vitro study models are based on cell culture in two dimensions (2D) since the investigation in these models are simple and can be easily reproduced. However, these systems have limitations such as false positive responses. Therefore, in order to clearly understand how neoplastic cells interact and behave, three-dimensional cell culture models (3D models) are under development. Thus, it emphasizes the importance that Tissue Engineering and nanotechnology represent for the development of biological models useful for understanding the processes of tumor progression, as well as resistance to therapies. In view of the need to develop more effective therapies, studies propose Photodynamic Therapy (PDT) as a promising therapeutic modality that uses three essential elements: a photosensitizer (FS), light at a specific wavelength and oxygen, reacting together to produce species reactive oxygen that ultimately cause cell death of target cells and tissues. Thus, the present project aims to develop a tumor dermal equivalent modified with spheroids of oral squamous cell carcinoma and to characterize it by histological and immunohistochemical techniques, to assess the presence of cytokines and matrix proteases by ELISA, to analyze the viability of spheroids and of the EDT via a resazurin assay. Then, phenyl-thio-phthalocyanine nanocapsules will be developed for the application of Photodynamic Therapy of oral carcinoma. Finally, apoptotic cell labeling will be performed after treatment with Annexin V and evaluation of the effect of PDT on three-dimensional tumor models in vitro. We hope to obtain a useful biological model for Tissue Engineering and antitumor therapy. (AU)