Politecnico di Torino | Servizi per la didattica

KEYWORD

Area Engineering

Design and characterization of biomimetic and therapeutic nanocarriers inspired by exosomes secreted by metastatic colorectal cancer cells

keywords DRUG DELIVERY, EXTRACELLULAR VESICLES, NANOPARTICLES

Research Groups AA - Materials and Processes for Micro and Nano Technologies

Thesis type EXPERIMENTAL

Description Colorectal cancer (CRC) is one of the oncological malignancies with the highest incidence and mortality rates. The dominant cause for such a high death rate is at large associated to the development of metastatic diseases. Statistics indeed show that about 25% of CRC patients is already affected by metastasis in the moment of the primary tumor diagnosis and almost the 50% of the cases evolve towards the same direction. Several studies noticed that Extracellular Vesicles (EVs) secreted by CRC cells carry intercellular signals and promote the tumor cells colonization of distant organ-specific metastatic sites, like liver and lungs. In particular, tumor cells produce a much greater amount of vesicles than healthy cells, allowing significant cell-cell exchanges, since they carry with them incorporated proteins, DNA, mRNA and microRNAs. Cancer-derived EVs have also been observed to abundantly get internalized back in the cancer tissue that originated them. Thus, the research carried out in this Master Thesis will aim at developing more precise and effective treatments of CRC. In particular it aims to design nanocarriers which have the same ability as the exosomes to target cells, that are able to fuse with the plasma membrane of the targets and deliver their content in the cytoplasm. In this way the nanocarriers inspired to those exosomes could be ideated as tumor-targeted drug delivery systems. The Thesis will be focused on the design of lipidic formulations, inspired by exosomal membrane of human CRC cell line, which have been exploited in the preparation of liposomes and as vectors for therapuetic drugs or zinc oxide nanocrystals. Size and surface charge characterizations will be performed on the nanocarriers, to confirm the possibility of manipulating their surface properties and biological behaviour. Also the interaction of liposomes with the cell membrane will be studied in vitro on CRC cells and different processes of internalization should be identified, as well as specific targeting towards cancer cells and not against healthy counter parts. Overall, this work should prove how promising the combination of nanotechnologies and a bio-inspired approaches is in the customization of anticancer nanocarriers and their optimization in terms of drug encapsulation and targeted release and ultimately to achieve a more efficient cancer treatment. Il lavoro di tesi è sperimentale e si svolgerà nei laboratori di ricerca del Politecnico di Torino al DISAT presso il TNHLab