Down the nanoparticle hole: ¹⁰³Pd:Pd/Fe-oxide theranostic agents for image-assisted thermo-brachytherapy as alternative cancer treatment

Cancer is one of the leading causes of death worldwide and the number of cases is expected to keep increasing in the next years. Even though nowadays most employed cancer treatments in clinical practice (surgery, chemo-, and radiotherapy) are effective, they are still associated with multiple limitations and side effects. The main pitfall stays in their non-specificity to tumour cells, which leads to affecting healthy tissues. Therefore, alternative treatments able to overcome the oncologic challenges of the current treatment regimens by specifically treating only the cancer cells, be minimally invasive, and limit short and long-term side effects are highly needed. As the number of patients diagnosed with cancer in incipient stages is constantly increasing, such alternative treatments are currently even more attractive. Due to the advances in nanotechnology, cancer nanomedicine is a fast-advancing field, employing nanoparticles to both diagnose and deliver therapy of cancer, namely, nanotheranostics. Nanobrachytherapy is the brachytherapy treatment delivered via injection of radioactive nanoparticles into the tumour. The great advantage is that nanobrachytherapy retains the characteristics of brachytherapy, such as precise and targeted dose delivery, while allowing a less invasive administration and a more uniform dose distribution in the tumour. However, the radio-resistance exhibited by the tumour cells can hinder the success of nanobrachytherapy, but the synergetic combination of cell damaging agents, as well as radioactivity and heating, is wellknown. Thermal treatments, such as hyperthermia, offer a hyperthermic radiosensitization making the tumour more susceptible to irradiation, while thermal ablation can serve as surgery replacement. Furthermore, thermal treatments can be delivered by injection of colloidal suspensions of magnetic nanoparticles (MNPs) in tumours and heating them via exposure to an externally applied alternating magnetic field. An additional advantage of such magnetic nanoparticles is their ability to ensure visualization via magnetic resonance imaging (MRI), a non-invasive technique, helpful in monitoring the treatment effects. This thesis aims to develop a nanotheranostic agent, able to deliver therapeutic effects via radiation and heating, with additional imaging via magnetic resonance imaging. We envision the nanotheranostic as a core-shell hybrid nanoparticle in the form of 103Pd:Pd/Fe-oxide. The palladium core is radiolabelled with 103Pd radioisotope, responsible for the required radiation dose, whereas the iron oxide coating ensures hyperthermia/thermal ablation and imaging…