PhD defence by Murillo Longo – Niels Bohr Institute - University of Copenhagen

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PhD defence by Murillo Longo

Cancer is one of the biggest public health problems in the whole world. In 2014, about 585,720 Americans are expected to die of cancer, almost 1,600 people per day. Cancer is the second most common cause of death in the US, exceeded only by heart disease, accounting for nearly 1 of every 4 deaths. Anyone can develop cancer. Since the risk of being diagnosed with cancer increases with age, most cases occur in adults who are middle aged or older. The disease is caused by both external factors (tobacco, infectious organisms, chemicals, and radiation) and internal factors (inherited mutations, hormones, immune conditions, and mutations that occur from metabolism). These causal factors may act together or in sequence to initiate or promote the development of cancer. Cancer is treated with surgery, radiation, chemotherapy, hormone therapy, immune therapy, and targeted therapy. In the case of chemotherapy, Paclitaxel is one of the most effective anti-cancer drugs currently available, however it causes a number of undesirable side effects.

The main goal of this work was to develop a new drug carrier that will help reducing these side effects. To achieve such objective the synthesis methodology of a bio-nanocomposite (bio-NCP) that combines the magnetic properties of Mn-Zn ferrite nanoparticles to the biocompatibility of chitosan and hydroxyapatite was developed and the drug was encapsulated. Subsequently, characterization of the drug delivery system was carried out using state-of-the-art solid-state tools, such as synchrotron and neutron diffraction, Near Edge X-Ray Absorption Fine Structure (NEXAFS) and neutron scattering spectroscopies. From the images obtained using Scanning Transmission X-ray Microscopy (STXM), we were then able to show that the drug carrier has a core-shell like structure and a study comparing the vibrational spectra of the pure drug to the one obtained for the encapsulated and released ones was performed. Using density functional theory (DFT) we were able to get initial information on the interactions between the encapsulation and the drug, which will allow, in the future, for designing drug carriers with reduced influence in the drug dynamics. Finally, results of in-vitro tests performed with macrophages indicate the low toxicity of the bio-NCP, since no immune response was detected.