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Development of Ultra-Sensitive Nanotherapeutic Anticancer Agents for Boron Neutron CaptureTherapy

Periodic Reporting for period 1 - NANOTER (Development of Ultra-Sensitive Nanotherapeutic Anticancer Agents for Boron Neutron CaptureTherapy)

Reporting period: 2016-10-01 to 2018-09-30

Cancer is one of the most relevant diseases worldwide because of its incidence, prevalence, and mortality. Current cancer treatments do not only kill cancer cells but also healthy tissue, causing severe secondary effects. In order to overcome this situation, more effective and selective treatments are necessary. Neutron capture therapy (NCT) is a biologically targeted form of radiotherapy which exploits the potential of some specific isotopes to capture thermal neutrons producing charged particles suitable for the cancer treatment. The range of the particles produced in NCT can be limited to the size of one cell. Therefore, provided that neutron capture species are selectively delivered to tumour cells, no damage will occur to the surrounding healthy tissue. Novel delivery agents suitable for NCT must be investigated that will allow a localized cancer treatment. NANOTER presents an innovative and previously unexplored approach to develop ultra-sensitive nanotherapeutic agents for NCT. High concentration of Neutron capture species (enriched boron counponds) were sealed in the interior of carbon nanocapsules and their behavior against neutron irradiation experiments was investigated and compared against other current materials for NCT. The external surface of the filled carbon nanocapsules were functionalized in order to increase the water dispersibility and cellular biocompatibility. The interdisciplinary approach taken to develop the proposed research programme is expected to contribute to the development of alternative and previously unexplored nanoplatforms for NCT, enhancing the performance of current delivery agents for NCT. The final aim of this project was to create novel NCT agents with improved cancer therapeutic efficacy, that can be successfully translated into preclinical studies.
Cancer is one of the most relevant diseases worldwide because of its incidence, prevalence and mortality. Current cancer treatments do not only kill cancer cells but also healthy tissue, causing severe secondary effects. In order to overcome this situation, more effective and selective treatments are necessary. Neutron capture therapy (NCT) is a biologically targeted form of radiotherapy which exploits the potential of some specific isotopes to capture thermal neutrons producing charged particles suitable for the cancer treatment. The range of the particles produced in NCT can be limited to the size of one cell. Therefore, provided that neutron capture species are selectively delivered to tumour cells, no damage will occur to the surrounding healthy tissue. Novel delivery agents suitable for NCT must be investigated that will allow a localised cancer treatment. NANOTER presents an innovative and previously unexplored approach to develop ultra-sensitive nanotherapeutic agents for NCT. In this work high concentration of Neutron capture species (enriched boron and lithium) were sealed in the interior of carbon nanocapsules and their behaviour against neutron irradiation experiments were investigated and compared against other current materials for NCT. The external surface of the filled carbon nanocapsules were functionalized in order to increase the water dispersibility and cellular biocompatibility. Biocompatibility tests of carbon nanocapsules with rat osteosarcoma UMR-106 cell line showed high levels of cellular viability. The interdisciplinary approach taken to develop the proposed research programme is expected to contribute to the development of alternative and previously unexplored nanoplatforms for NCT, enhancing the performance of current delivery agents for NCT. The final aim of this project is to create novel NCT agents with improved cancer therapeutic efficacy, that can be successfully translated into preclinical studies.
The aim of the research programme developed for NANOTER is to go beyond the state-of-the-art in the exciting field of NCT by designing a novel nanocarrier platform that can encapsulate unprecedented amounts of neutron capture active species. The proposed system is robust and highly versatile; therefore is expected a notorious improvement of the performance with respect to current benchmark systems. The possibility of delivering a highly localised amount of energy to tumour cells without affecting surrounding healthy tissues will represent a step-forward not only with respect to current state-of-the-art NCT platforms but also with respect to the classical cancer therapies like external and internal radiotherapy, chemotherapy or surgery.
The novel synthetic methodologies and characterization skills to be developed and enhanced throughout the duration of the project will provide the researcher with additional skills that will help to boost his career as an independent experienced scientist. The advanced and multidisciplinary training program designed for the researcher combines several research and training activities, including secondments in top international laboratories at the forefront of research, access to state-of-the-art facilities to carry out advanced experiments, and a number of training activities. The researcher will be also provided with the possibility of supervising and mentoring young fellow researchers. Besides, he will be able to build on existing and/or novel national and international collaborations through the development of his research project and provide a major contribution to international conferences with oral talks and/or poster presentations.